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Abstract

  1. Top of page
  2. Abstract
  3. Electrical Stimulation in CP
  4. Review of the literature
  5. Common Themes and Limitations of Prior Studies
  6. The Need for Better Devices and the Implanted Microstimulator
  7. Arm Rehabilitation Study
  8. Features for an Electrical Stimulation System in CP
  9. Development of an Implanted Battery-Powered Microstimulator
  10. Conclusions
  11. References

Electrical stimulation (ES) for treatment of neuromuscular disorders is introduced. Various forms of ES are defined. Characteristics of cerebral palsy (CP) and treatment options are given. The clinical objectives of ES for CP treatment are stated. A review of the literature for treatment in CP is given. Several common themes within the literature and limitations in prior studies are explored. The majority of studies have used surface stimulation, which has several inherent limitations. To address these limitations, implanted devices may be used. Implanted device systems include percutaneous stimulation systems, and fully implantable leaded systems. While both of these technologies have advantages over surface stimulation, they also have their own limitations. To further address the limitations of percutaneous and fully implantable leaded systems, the Alfred Mann Foundation has developed a completely implantable, telemetered device known as the Radio Frequency Microstimulator (RFM). Results from a study using the RFM for arm rehabilitation in poststroke patients are given. A list of desirable design features for an ES system for CP is given. The next generation microstimulator device under development at the Alfred Mann Foundation is presented. This device may well serve the needs for ES in CP.

LIST OF ABBREVIATIONS
ARAT

Action research atom test

ES

Electrical stimulation

FEBPM

Functional Electrical Stimulation Battery-Powered Microstimulator

FES

Functional electrical stimulation

FM

Fugl–Meyer

MCU

Master control unit

NMES

Neuromuscular electrical stimulation

P-FES

Percutaneous FES

RFM

Radio Frequency Microstimulator

ROM

Range of motion

TA

Tibialis anterior

TES

Threshold electrical stimulation

Electrical stimulation (ES) of nervous tissue may be used to trigger action potentials in axons by artificially depolarizing some portion of the axon membrane to threshold. When ES is applied appropriately to the motor nerves that innervate skeletal muscle, it can induce muscle contraction. Repetitive ES of these motor nerves is an efficacious therapy for patients with various neuromuscular disorders, including stroke1–8 and spinal cord injury.9–11 The potential therapeutic effects of ES have both peripheral and central components. Peripherally, ES acts to strengthen muscles,12 reduce spasticity of the antagonist muscle,13 reduce spasticity of the stimulated muscle,14 reduce co-contraction,15 and create soft-tissue changes that allow increased range of motion (ROM).16 Centrally, stimulation enhances reorganization in the motor regions of the brain by an effect known as plasticity.17–24 It is often unclear how much of the effectiveness of ES in various disorders is due to central versus peripheral mechanisms.

Motor learning theory asserts that for motor learning to occur, activities must be repetitive, goal-oriented, and at the limit of performance.25–27 De Kroon’s review,28 examining the relationship between stimulation parameters and methods of application and improvement in upper-limb function in poststroke hemiplegia, demonstrated that the only factor making a significant difference was voluntary activation of stimulation. The conventional wisdom is that to promote central mechanisms of central nervous system (CNS) plasticity, stimulation should be: (1) highly repetitive; (2) task-specific (physiologically relevant); (3) cognitively oriented; (4) novel (i.e. the individual cannot do it alone); (5) at the limit of performance; and (6) combined with feedback of performance.

Definitions of the various forms of electrical stimulation are not consistent throughout the literature. A review article by Kerr et al.29 offers the following definitions, which will be used herein. Neuromuscular electrical stimulation (NMES) is the application of an electrical current of sufficient intensity to elicit muscle contraction. Two strengthening mechanisms are proposed for the therapeutic effects of NMES: (1) the overload principle, resulting in greater muscle strength by increasing the cross-sectional area of the muscle; and (2) selective recruitment of type II fibers (fast-twitch, large diameter fibers), causing improved synaptic efficiency of the muscle.30,31 When NMES is applied in a task-specific manner, in which a muscle is stimulated when it should be contracting during a functional activity, it is referred to as functional electrical stimulation (FES). Threshold electrical stimulation (TES), also known as therapeutic electrical stimulation, is distinct from NMES. TES is a low-level, subcontraction electrical stimulus that is typically applied at home during sleep. Pape32 proposed that increased blood flow during a time of heightened hormone secretion (during sleep) results in increased muscle bulk.

Electrical Stimulation in CP

  1. Top of page
  2. Abstract
  3. Electrical Stimulation in CP
  4. Review of the literature
  5. Common Themes and Limitations of Prior Studies
  6. The Need for Better Devices and the Implanted Microstimulator
  7. Arm Rehabilitation Study
  8. Features for an Electrical Stimulation System in CP
  9. Development of an Implanted Battery-Powered Microstimulator
  10. Conclusions
  11. References

Cerebral palsy (CP) is defined as brain damage occurring before 2 years of age and causing motor dysfunction. It is non-progressive. CP has multiple causes. An estimated two per 1000 people in the developed world have CP.33–35 CP is generally present at birth, but may not be detected until up to 3 years of age. Characteristics of CP include: (1) stiff or tight muscles, and an associated increase in tonic stretch reflex (spasticity); (2) lack of muscle coordination when executing voluntary movement (ataxia); (3) walking with one foot or leg dragging; (4) walking on the toes; (5) a crouched gait or ‘scissored’ gait; (6) muscle tone that is either too stiff or too flaccid; (7) difficulty articulating speech (dysarthria); and (8) difficulty swallowing (dysphagia).

Treatment options in CP consist of: (1) physical and occupational therapy: spasticity can prevent stretching, and muscle growth may not keep up with bone growth. Range-of-motion exercises prevent muscles from becoming weak or rigidly fixed from contracture; (2) orthotics, to help to control limb position and stretch the spastic muscle; (3) speech therapy, to help develop communication and swallowing; (4) mechanical aids, such as Velcro shoe straps, motorized wheelchairs, and computerized communication devices; (5) drugs to control spasticity, such as diazepam (Valium; Roche Laboratories, Nutley, NJ, USA), dantrolene, phenobarbital, baclofen (a muscle relaxant and antispastic), and botulinum toxin (Botox: Allergen, Irving, CA, USA); and (6) electrical stimulation of skeletal muscle.

Treatments for spasticity include weakening the spastic muscles using oral agents or injectable agents such as botulinum toxin A; surgical treatments, including tendon transfer to balance the spasticity or selective rhizotomy; strengthening the antagonist muscle with electrical stimulation; physical therapy; and stretching the spastic muscle with an orthosis.

The clinical objectives in electrical stimulation with CP include: (1) reduction of stiffness and exaggerated reflexes (spasticity); (2) reduction of co-activation (co-contraction) of antagonistic muscles; (3) increasing the ROM; (4) muscle strengthening to fill the gap that patients experience as an inability to fully activate their muscles (poor percentage recruitment of muscle fibers); (5) muscle strengthening to increase impulse during walking; and (6) improving the timing of coordinated movement.

Review of the literature

  1. Top of page
  2. Abstract
  3. Electrical Stimulation in CP
  4. Review of the literature
  5. Common Themes and Limitations of Prior Studies
  6. The Need for Better Devices and the Implanted Microstimulator
  7. Arm Rehabilitation Study
  8. Features for an Electrical Stimulation System in CP
  9. Development of an Implanted Battery-Powered Microstimulator
  10. Conclusions
  11. References

A small number of studies have been published studying electrical stimulation in CP to reduce spasticity in the upper extremity and improve hand function. In 1997, Carmick36 published a case report on the use of NMES and a dorsal wrist splint to improve hand function of a child with spastic hemiparesis. After 1 year without physical therapy and NMES, the child returned for physical therapy with NMES. He quickly regained his previous level of functioning and made additional progress. Carmick concluded that the benefit of the splint was that wrist flexion decreased, allowing the child the chance to learn grasp, release, and opposition functions independently without anyone holding the wrist position; thus, motor learning could occur because the wrist extensors were held in a shortened position.

Scheker et al.15 reported on NMES and dynamic bracing as a treatment for upper-extremity spasticity in children with CP. The use of an orthosis alone to stretch the spastic muscle addresses the static component of spasticity (muscle shortening), but not the dynamic component (abnormal tone and imbalance). In this study, 19 children with CP were treated with the combined therapies. Surface NMES was applied to the antagonist wrist and finger extensors combined with dynamic orthotic traction during the day; a static brace was used at night. Treatment ranged from 3 to 43 months. All patients moved up from one to three levels in the Zancolli classification and showed improvement in upper-extremity function.

Wright and Granat16 reported on the therapeutic effects of FES of the upper limb of eight children with CP. Cyclic FES was applied to the wrist extensors for 6 weeks. Improvements were observed in hand function and active wrist extension. Improvements were largely maintained until the end of the follow-up period. The improvements in active wrist extension suggest that exercise of the wrist extensors with FES increases the strength of the muscle and; therefore; the joint ROM, where the soft tissue around the joint permits further movement.

Ozer et al.37 reported on NMES and dynamic bracing for the management of upper-extremity spasticity in children with CP. This study compared the combined use of NMES and dynamic bracing with either treatment option alone. Twenty-four patients with hemiplegic CP were in the study. Participants were divided into three groups: Group 1 had two 30-minute sessions of NMES per day applied to the antagonist extensors without bracing; Group 2 had two 30-minute sessions of dynamic bracing per day; and Group 3 received both. Treatment lasted 6 months. Significant improvements were found in all measures only for patients receiving both treatment modes; however, these improvements lasted for only 2 months after discontinuation of treatment.

Kamper et al.38 reported on the effects of NMES treatment with respect to potential impairment mechanisms. This pilot study evaluated eight patients with CP who received 3 months of NMES targeting wrist flexor and extensor muscles. The goal was to examine quantitatively the impact of NMES on potential impairment mechanisms. Surface stimulation was applied to the wrist extensors and flexors. Seven of eight participants demonstrated significant improvement in wrist extension ROM as well as extensor strength. Differences in spasticity and passive resistance were not significant. The authors concluded that the observed increase in isometric wrist-extension torque likely arises from reduced flexor co-activation.

Barbosa et al.39 evaluated the therapeutic effects of ES on manual function of two children with CP. Children with CP develop movement disorders not only because of the primary neurological deficit but also because of secondary adaptations.40 Muscle weakness and alterations in passive stiffness are common. Stimulation of the wrist extensors or extensors and flexors was performed in two children using surface stimulation. Significant performance gains were observed in both children, especially with combined extensor and flexor stimulation. Performance decreased after intervention withdrawal, which is different from the result observed by Wright and Granat16 who reported maintenance during a 6-week follow-up after stimulation.

Electrical stimulation for treatment of lower-extremity function in CP has received more attention than for the upper extremity. Carmick41 reported on the clinical use of NMES for children with CP. NMES was applied to the lower extremities of three children, using different muscles. This was used with a task-oriented model of motor learning, along with physical therapy. All three children demonstrated rapid functional changes. Two children demonstrated carryover after removal of the NMES (reported as 4wks in case 1 and 1y in case 2).

Dubowitz et al.42 reported on chronic electrical stimulation of two children with hemiplegic CP. The tibialis anterior was stimulated during activity. Motor performance and gait improved after a few weeks of stimulation.

Daichman et al.43 reported a case study on the effects of an NMES home program on impairments and functional skills of a child with spastic diplegic CP. They concluded that NMES may allow a child with poor motor control to participate in a progressive strength-training program. NMES may also lead to motor learning. Daichman et al. studied the effects of NMES applied to the quadriceps every other day for 6 weeks. After treatment, quadriceps strength increased substantially but hamstring spasticity decreased. The child demonstrated several newly attained skills.

Van der Linden et al.44 evaluated ES of the gluteus maximus in children with CP and effects on gait characteristics and muscle strength. Gluteus maximus stimulation was studied in 22 children for the purpose of improving hip extensor strength, decreasing excessive passive and dynamic internal hip rotation, and improving gross motor function. Eleven children were in the stimulation group and eleven were in the control group. Surface stimulation was used. No statistically or clinically significant improvement was found. However, the parents of seven of the 11 treated children thought treatment made a difference. The authors noted that one problem was ‘the gluteus maximus is a more difficult muscle to stimulate than, for example, the tibialis anterior, because of its greater mass and its covering of adipose tissue.’44

Johnston et al.45 evaluated the use of FES to augment traditional orthopaedic surgery in children with CP. This was a comparison of functional outcomes of traditional lower-extremity orthopaedic surgery (lengthening and/or release of spastic muscles) to more-limited surgery augmented with FES applied while walking. Seventeen children with CP were evaluated, with nine in the surgical group and eight in the FES group. Percutaneous intramuscular electrodes were implanted. One year after intervention all children showed improvement, with no significant difference between groups. Children in the FES group, however, underwent an average of 4.5 fewer ablative procedures. There was a trend for FES participants to recover more quickly. One electrode was removed during the year because of an infection that tracked along the length of the electrode.

Pierce et al.46 reported a comparison of percutaneous and surface FES during gait in a case report of a child with hemiplegic CP. This study compared the immediate effects of surface versus percutaneous FES of the TA. Surface FES was controlled by a commercial foot switch in the heel of the shoe, and percutaneous FES was controlled by force-sensing resistors in the insole of the shoe. The increase in dorsiflexion was greater with percutaneous FES (P-FES). The authors speculate that a stronger muscle contraction was recruited with P-FES as the patient could tolerate greater activation as cutaneous receptors were not activated.47,48 Pierce et al.49 evaluated the direct effect of P-FES during gait in two children with hemiplegic CP. They used percutaneous stimulation of the gastrocnemius only, the TA only, or both, for the purpose of improving ankle kinematics and kinetics during gait. Stimulation was triggered during the gait cycle using force-sensing foot switches. Both children showed immediate improvements when using TA only or combined TA/gastrocnemius stimulation.

Orlin et al.50 reported on the immediate effect of percutaneous intramuscular stimulation during gait in eight children with CP. They evaluated percutaneous intramuscular FES for immediate improvement of ankle kinematics during gait. Stimulation was to the gastrocnemius, the TA, or both, during the appropriate phase of gait and was triggered by force-sensing resistors in the shoe insole. After 1 week of stimulation, significant improvements occurred in the gastrocnemius/TA combined condition and the TA-only condition.

Postans and Granat51 reported on the effect of FES, applied during walking, on gait in spastic CP. Eight children with CP received FES during walking using individualized stimulation programs. Clinically significant improvements occurred in three of the eight children.

Ho et al.52 reported that FES changes dynamic resources in children with spastic CP. Their objective was to study the effects of surface FES applied to the gastrocnemius-soleus complex. They studied immediate effects only. FES was triggered with a foot switch. Thirteen children with CP and six children who were developing normally were evaluated. The 13 children with CP either performed 15 trials with FES followed by 15 without, or vice versa. Normally developing children performed 30 trials. Children with CP undergoing FES had a significantly greater speed-normalized dimensionless impulse. There was no significant difference in normalized stiffness between the children who were developing normally and the CP children in either the FES or no-FES condition. The authors conclude that FES is effective in increasing impulse during the push-off phase of the gait cycle, but not in decreasing stiffness. The effects on increasing impulse did not result in more typical spatiotemporal gait parameters.

Kerr et al.53 performed a randomized, controlled trial of ES in CP. NMES and TES were used to strengthen the quadriceps in 60 children with CP. Eighteen children were in the NMES group, 20 in the TES group, and 22 in the placebo group. NMES was applied for 1 hour per day, 5 days per week, and TES was applied 8 hours per night for 5 nights/week. No statistically significant difference in strength or function was observed for either NMES or TES versus placebo. Statistically significant differences were found between both NMES and TES versus placebo for impact on disability at the end of 16 weeks of treatment, but only between TES and placebo at the end of 6-week follow-up. The authors concluded that ‘the use of surface electrodes resulted in the stimulation of nociceptors, consequently limiting the intensity of stimulation to patient tolerance and reducing the level of muscular contraction attainable.’53 Of interest is that these authors used an objective measure of compliance with ES programs (using a timer in the stimulator), and the recorded compliance was substantially lower than that previously self-reported.

Kang et al.54 assessed the additive effect of adjuvant ES (surface stimulation on the gastrocnemius) on botulinum toxin A (BoNT-A) injection for spastic calf muscles in children with CP. Partial denervation of spastic muscle by BoNT-A diminishes hyperexcitability and hypertonicity and improves motor control and gait ability. Also, relaxation of spastic muscles facilitates limb growth and reduces the frequencies of fixed contractures. ES improves ROM, strengthens muscle, and reduces spasticity. It also accelerates the internalization of BoNT-A into the nerve terminals.55 Stimulation was applied for 30 minutes, twice per week, for 2 weeks. Eighteen children with CP dynamic foot equinus were injected with BoNT-A into the calf; seven of these participants also received electrical stimulation. A significant increase in passive ROM was noted 2 weeks after injection in the treatment group and after 3 months in both groups. Subscales of the Physician’s Rating Scale were significantly improved in the treatment group, but not in the control group, 3 months after injection. The authors concluded that adjuvant electrical stimulation for a short period after BoNT-A injection had a positive effect on early improvement in ROM and maintenance of gait.

Stackhouse et al.56 performed a preliminary study to compare volitional isometric strength training versus isometric NMES in children with spastic diplegic CP. This was an evaluation of NMES to increase muscle strength in CP using high-force contractions with low repetitions. Low muscle force in children with CP may be caused by decreased CNS motor unit recruitment and discharge rates, increased antagonist co-activation during agonist contractions, and changes in muscle morphology, including atrophy. There has been a bias against strength training for patients with CNS dysfunction because of the unsubstantiated belief that high-effort voluntary contractions may increase muscle spasticity. The NMES technique used in this study entailed implanting percutaneous electrodes in the quadriceps femoris and triceps surae. Eleven children with CP were assigned to either an NMES group or volitional group (who trained with maximal effort contractions). A 12-week isometric strength-training program was used. High forces were used (≥50% of maximum voluntary isometric contraction force) with low repetitions (1×15, 15s on and 45s off, thrice weekly). The NMES group had greater increases in normalized force production in both muscle groups, and only the NMES group had increased walking speed. The authors hypothesized that the increased force production with NMES is due to the ability to train at force levels beyond what can be produced volitionally.

Katz et al.57 reported on enhancement of muscle activity by ES in CP as a case-control study. The objective was to compare the effects of low-level stimulation of the quadriceps in children with CP under two conditions: reconditioning by long-term training of the muscle versus real-time assist to the muscle during motion (‘neural orthosis’ mode). In the long-term mode, the muscle has been reported to undergo fiber transformation from fast- to slow-twitch, increasing in strength and decreasing spasticity.58 In the neural orthosis mode, muscle force is increased because of the combined effects of volitional and electrically assisted activation. Five children were evaluated. Surface stimulation was used. There was a significant increase in motion velocity and a decrease in motion jerk in both modes. There was a significant decrease in quadriceps-hamstrings co-contraction following long-term training, but not during stimulation-assisted motion. The authors concluded that long-term training is a more beneficial form of ES than real-time assist.

Van der Linden et al.59 studied FES applied to the ankle dorsiflexors and quadriceps in 14 children with CP. The objective of the study was to compare orthotic versus therapeutic effects of FES. The treatment group had 2 weeks of NMES followed by 8 weeks of FES. The control group received usual physical therapy. FES of the ankle dorsiflexors resulted in a significant orthotic effect on gait kinematics in both groups; however, no long-term treatment effect of using FES for 8 weeks was found.

Threshold electrical stimulation (TES), defined as low-level, subcontraction electrical stimulation, has been hypothesized to increase muscle strength through an increase in muscle blood flow, although there is no muscle contraction.32 The results from a small number of TES studies are inconsistent.

Pape et al.60 reported on six CP children with spastic hemiplegia or diplegia who received overnight TES to the leg muscles. After 6 months of treatment, significant improvements were observed in gross motor, locomotor, and receipt/propulsion skills. Six months after treatment withdrawal, the improvements diminished, but reinstitution of TES resulted in further significant improvements.

Steinbok et al.61 performed a randomized, controlled trial using overnight TES on children with CP who had undergone selective posterior lumbosacral rhizotomy more than 1 year previously. The treatment group received TES for 1 year; the control group received no TES. There was a significant improvement in Gross Motor Function Measure for the treated group.

Sommerfelt et al.62 performed a randomized, controlled trial using TES in 12 children with CP. They evaluated TES applied to antagonists of spastic leg muscles using surface stimulation in this 24-month crossover study. Six children received TES during the first 12 months, and six received TES for the second 12 months. Children slept with the TES for a minimum of 5 hours per night. No significant effect of TES on motor or ambulatory function was found on blinded evaluation, although parents of 11 of 12 children reported that TES had a significant effect.

Dali et al.63 studied TES in ambulant children with CP as a randomized, double-blind, placebo-controlled trial involving 57 children. Two-thirds of the children received active stimulators and one-third received inactive stimulators. The treatment group received 12 months of TES. Stimulation was applied to the quadriceps femoris and TA. There was no significant difference between the treatment and placebo groups. There was a general increase in quadriceps area, but no definite TES pattern emerged.

Common Themes and Limitations of Prior Studies

  1. Top of page
  2. Abstract
  3. Electrical Stimulation in CP
  4. Review of the literature
  5. Common Themes and Limitations of Prior Studies
  6. The Need for Better Devices and the Implanted Microstimulator
  7. Arm Rehabilitation Study
  8. Features for an Electrical Stimulation System in CP
  9. Development of an Implanted Battery-Powered Microstimulator
  10. Conclusions
  11. References

Prior studies of ES have mostly used surface stimulation. This approach is associated with difficulty in obtaining repeatable stimulated responses, an inability to stimulate deeper muscles, stimulation of unintended muscles, and decreased skin tolerance with prolonged use.64 Surface stimulation also routinely causes stimulation of cutaneous nociceptors.47,48

An observation apparent to any reviewer of the CP literature, and in fact pointed out in numerous articles in the primary literature, is that there have been no standards for electrical stimulation, including stimulator parameters, frequency of use, and outcome measures.

Kerr et al.29 published a review on the effects of ES on strength and motor function in individuals with CP. Of 12 studies evaluated for NMES, one reported no improvement, one was inconclusive, and 10 showed improvements in function and/or strength. These authors made the following four notable observations: (1) The scarcity of well-controlled trials makes it difficult to support definitively or discard the use of ES in the pediatric CP population. The research is dominated by case studies and uncontrolled studies. (2) No authors cited specific guidelines with regard to their choice of parameters. (3) Several authors reported parent/carer perceptions of treatment effects that were not always supported by the study results. (4) In conclusion, it seems there is more evidence to support the use of NMES than TES. However, the findings of the studies must be interpreted with caution because they generally had insufficient statistical power to provide conclusive evidence for or against these modalities. Further studies employing more rigorous study designs and follow-up, larger sample sizes, and homogeneous patient groups are required for the unequivocal support of the use of electrical stimulation.29

A common finding in studies of ES for upper-extremity spasticity is that the therapeutic effects decrease after cessation of therapy.16,65–68

The Need for Better Devices and the Implanted Microstimulator

  1. Top of page
  2. Abstract
  3. Electrical Stimulation in CP
  4. Review of the literature
  5. Common Themes and Limitations of Prior Studies
  6. The Need for Better Devices and the Implanted Microstimulator
  7. Arm Rehabilitation Study
  8. Features for an Electrical Stimulation System in CP
  9. Development of an Implanted Battery-Powered Microstimulator
  10. Conclusions
  11. References

Surface electrical stimulation, using electrodes applied to the skin, is well established within the primary literature. The advantages of the technique are: that it does not require surgery; and it can be applied in the home by the patient or caregiver.

Disadvantages of surface electrical stimulation are as follows: (1) High levels of charge (e.g. 100+ mA for 0.2ms) are often used. This may result in pain as cutaneous nociceptors are collaterally stimulated; (2) It is relatively non-selective, often stimulating untargeted muscles; (3) It may not stimulate all the intended muscles, especially deep muscles; (4) Significant patient assistance may be required to don and doff the equipment; and (5) Accurate placement of electrodes over motor points to achieve repeatable motor responses is challenging.

Implanted neurostimulation devices consist of metal electrodes implanted close to either motor nerves or the motor points where muscle is innervated. These devices mitigate many of the disadvantages of surface stimulation. By placing the stimulating electrode close to the desired target, implanted devices gain two important advantages:

They require substantially less charge (0.5–3mA for 0.2ms); and stimulation is selective.

One popular approach is to use electrodes attached to percutaneous (across the skin) leads. The leads connect implanted electrodes to an external pulse generator. These systems suffer from two disadvantages: the percutaneous leads present a persistent infection route; and the leads may fatigue and break, requiring additional surgical interventions.

Several studies reviewed in this work45,46,49,50 that have demonstrated the benefits of percutaneous stimulation have been published by researchers at Shriner’s Hospitals for Children in Philadelphia, Pennsylvania.

Another implanted technology is the use of fully implanted, leaded systems. These systems use an implanted central pulse generator that is connected to several distributed electrodes by leads. An example is the Freehand system.69 Such systems have the following disadvantages: the surgeries are lengthy and highly invasive; the systems are not intended for short-term therapeutic use; the long leads must be robust, as they may move across joints or hard surfaces; and any infection may be propagated along the leads.

The Alfred Mann Foundation has developed a system that mitigates the problems of both percutaneous and fully implanted leaded systems. This system consists of a wireless, implantable neurostimulator known as the Radio Frequency Microstimulator (RFM). These devices may be surgically implanted next to nerve or motor points in a minimally invasive procedure. Because the system is wireless, the problems of infection and lead breakage are mitigated. The RFM, shown in Figure 1, is a hermetically sealed, implantable device. It has a cylindrical shape, 16.6mm long and 2.4mm in diameter. The case consists of ceramic (zirconia stabilized with 3mol% yttria). At one end of the device is an iridium disk that acts as a cathode. During surgery this end is placed near a motor point. At the other end of the device is the anode. The anode collectively consists of a ferrule and end cap, both consisting of Ti-6-4 (90% titanium, 6% aluminum, 4% vanadium), and a 90/10 platinum-iridium eyelet. Case strength, hermeticity, corrosion resistance, and biocompatibility have been reported previously.70,71 The eyelet allows the surgeon to attach a length of suture to the device and to retrieve it within the first days after implantation should the device migrate away from the motor point.

image

Figure 1.  External features of the radio frequency microstimulator. Material composition of the components is shown. All materials are well demonstrated as biocompatible.

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Inside the RFM are a coil, which receives power and commands from a second coil that is external to the patient, and the custom microelectronics necessary to form DC power, decode the commands, and drive current pulses between the cathode and anode. The internal and external coils communicate wirelessly by an inductive (magnetic) link. The external coil delivers power and commands to the RFM using a center carrier frequency of 2.00MHz (2 million cycles per second) ±50KHz. This carrier signal is modulated by command data using amplitude shift keying. The command data include addresses for the RFMs (up to 255 devices may be driven) and pulse amplitude, pulse width, and frequency for each RFM. The system uses a one command-one pulse scheme. There is no autonomous mode. The RFM will stimulate only when it is commanded to do so. The power and modulated pulsing data are sent to the external coil from a control unit cabled to the coil. The high-efficiency transmitter driver topology has been described elsewhere.72

The stimulating pulses are charge-balanced biphasic current pulses, asymmetric, using trickle anodic charge recovery, as shown in Figure 2. Compliance voltage is 15V minimum. The pulse amplitude ranges from 0.228mA to 3.5mA in 0.27mA increments, and 5.4mA to 40mA in 2.7mA increments. The pulse width ranges from 2 to 513μs in 2μs increments. The recharge current is selectable at 0, 10, 100, or 500μA. The pulse repetition rate is up to 650 pulses per second per device.

image

Figure 2.  Stimulation pulse parameters. Pulsing is charge balanced, asymmetric biphasic current pulsing using trickle anodic charge recovery.

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After the RFM has been implanted, the clinician performs a fitting session to set the stimulation parameters for each microstimulator (including pulse amplitude, pulse width, frequency, ramp time, and recharge current), sequences of stimulation based on uniquely addressed RFMs, and triggers based on external triggers or switches. The fitting session is done using a laptop computer, known as the fitting system. Once the stimulation parameters have been determined, this information is downloaded from the fitting system to the control unit. The patient does not have access to the fitting system, but may choose from one of three programs downloaded to the control unit. The control unit has a sensor port, allowing up to four channels of sensors or switches to trigger the sequencing of the microstimulators.

The first generation of these devices consisted of electronics hermetically sealed into a glass package. The devices were used to treat shoulder subluxation in stroke patients and patients with knee osteoarthritis73,74 and in patients with poststroke hand contractures.75 In the second generation, the glass was replaced with a ceramic package. These devices have been used in the treatment of obstructive sleep apnea, poststroke shoulder subluxation,76 and poststroke arm rehabilitation.8

Arm Rehabilitation Study

  1. Top of page
  2. Abstract
  3. Electrical Stimulation in CP
  4. Review of the literature
  5. Common Themes and Limitations of Prior Studies
  6. The Need for Better Devices and the Implanted Microstimulator
  7. Arm Rehabilitation Study
  8. Features for an Electrical Stimulation System in CP
  9. Development of an Implanted Battery-Powered Microstimulator
  10. Conclusions
  11. References

A recent application of the RFM system was a feasibility study developed in collaboration between the Alfred Mann Foundation and clinical partners at the University of Southampton, UK, to investigate the use of implanted RFMs for recovery of upper-limb function in poststroke patients. In this study, implanted RFMs were used to repetitively activate upper-limb muscles in a physiological-like sequence. This allowed evaluation of therapeutic outcomes, potentially by enhancing central mechanisms of plasticity. Surface stimulation has successfully been used for recovery of upper-limb function in stroke patients.7,77 Such stimulation has several disadvantages, as already noted. A specific problem is that surface stimulation cannot selectively activate wrist extensors and the muscles controlling finger and thumb extension and thumb abduction.

The arm rehabilitation study used a dual coil configuration for the external coil, with one coil over the upper arm and a second over the lower arm. To facilitate stimulation of the patient’s muscles that was synchronized to the sequence of his or her volitional movements, two external sensors were incorporated. The sensors consist of a commercially available goniometer to detect the elbow joint angle, and a touch pad to detect strike of the hand onto a table. The touch pad uses a resistive bridge compression load cell as the primary sensor. The load cell is placed into a well that is machined into the underside of a hard plastic mat. Flexion of the plastic mat, due to placement of a mass (the hand) or release of the mass, is coupled to the load cell. In addition to the external sensors, start and stop buttons are provided. The start button allows a patient to initiate stimulation sequences using the non-hemiplegic hand, and the stop button allows the patient to terminate a sequence.

The control unit uses four channels for sensor inputs. Control unit channel 1 is connected to the goniometer output after filtering and amplification. Control unit channel 2 represents the touch pad channel. Control unit channel 3 represents the state of the trigger buttons, and channel 4 represents the state of the stop buttons. The major components of the system are illustrated in Figure 3.

image

Figure 3.  Arm rehabilitation study system components. (a) Implant tools. (b) Radio frequency microstimulator (RFM) implant device. Note the RFM with suture to scale with the tools. (c) System used in phase 1 of the Arm Rehabilitation study.

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The study at Southampton was performed with seven poststroke participants with hemiplegia. All had had an ischemic stroke ranging from 1.1 to 10.5 years before recruitment for this study; mean time poststroke was 3.9 years. Each participant was implanted with between five and seven RFMs at appropriate motor points to elicit elbow, wrist, and finger and thumb extension and thumb abduction. The study was divided into three phases. The first phase consisted of the implant procedure and subsequent fitting session, followed by a 12-week period of at-home use, during which participants would turn on the control unit and commands were sent in an open-loop fashion to elicit elbow extension, wrist extension, finger and thumb extension, and thumb abduction. Participants would typically engage in half-hour sessions, up to 2 hours of total use per day, during which they would perform everyday tasks such as drinking from a cup.

In the second and third phases of the study, a triggering scheme was developed to allow a sequence of reaching for an object, grasping it, bringing it toward the body, extending the arm to put the object back, releasing the object, and bringing the hand back to the body. All motions were performed at the speed intended by the participant. As suggested by Schmidt and Lee25 optimal motor relearning is accomplished by repetitive, goal-oriented activities. In order to make the activity sequencing as close as possible to normal use, it was necessary to develop sensors to detect both the elbow joint angle (the goniometer) and the time when the hand struck the table (the touch pad). In phase two of the study, the parameters for stimulation were set up in the clinic, including the sequencing of various RFMs associated with distinct motor points, definitions of the trigger sources to initiate or terminate each activity sequence, delays between certain sequences, elbow joint angles for which the goniometer would cause activity sequence transitions, and sensitivity of the touch pad. In phase three of the study, participants used the system at home. During this 12 week period, participants used the triggered system for 1 hour per day, 5 days a week. After the stimulation period ended, participants went through a 12-week period without stimulation to allow evaluation of therapeutic carryover.

The primary outcome measure for upper-limb function was the action research arm test (ARAT) and the primary impairment measure was ability to perform a tracking test (motor control). Movement, coordination, and sensation of upper limb were measured using Fugl–Meyer (FM) upper-limb measurement. Resistance to passive movement was measured by the modified Ashworth scale.

Details of the therapeutic efficacy have been described.8 A mean improvement between baseline and 12 weeks was identified in all outcome measures. Functional improvement (ARAT) was measured in four of the seven participants, three of whom made clinically important changes. Impairments that improved tended to be those on which participants scored poorly at baseline. Improvement in impairment measures, such as the FM, active ROM, and motor control, was greater than that in functional measures, and this may be because impairment measures are more sensitive to change. Participants who improved most in terms of function were those whose strokes had occurred less than 2 years earlier. There was no relationship between total stimulation time and improvement in any outcome measures. The implications for this are that future studies should recruit participants sooner after stroke and that lower-functioning participants should not be excluded.

Features for an Electrical Stimulation System in CP

  1. Top of page
  2. Abstract
  3. Electrical Stimulation in CP
  4. Review of the literature
  5. Common Themes and Limitations of Prior Studies
  6. The Need for Better Devices and the Implanted Microstimulator
  7. Arm Rehabilitation Study
  8. Features for an Electrical Stimulation System in CP
  9. Development of an Implanted Battery-Powered Microstimulator
  10. Conclusions
  11. References

An electrical stimulation system for CP patients should have three important features. First, it should have no bulky external equipment, such as the coils of the RFM system. An easily worn, portable controller is desirable. Second, more compact or lighter-weight trigger mechanisms are worth consideration. One such trigger is the electromyogram (EMG), which has been shown to have some therapeutic benefits with surface and intramuscular stimulation.5,6 Although poststroke patients or patients with CP may be unable to generate acceptable force under fine control, they may retain sufficient muscular activity for EMG detection of contraction initiation. This detection could then be used to drive stimulation of the appropriate motor points, effectively enhancing a feeble initiation signal. Use of two EMG signals, one from each leg, might be used to determine the proper phase of gait. Third, the patient needs an easy way to turn the system on and off, giving a secure feeling of being in control. There remains a concern that the device may cause spasms in stimulated muscle; thus, the patient must be able to stop stimulation quickly.

Development of an Implanted Battery-Powered Microstimulator

  1. Top of page
  2. Abstract
  3. Electrical Stimulation in CP
  4. Review of the literature
  5. Common Themes and Limitations of Prior Studies
  6. The Need for Better Devices and the Implanted Microstimulator
  7. Arm Rehabilitation Study
  8. Features for an Electrical Stimulation System in CP
  9. Development of an Implanted Battery-Powered Microstimulator
  10. Conclusions
  11. References

While the RFM system has mitigated problems inherent in surface and percutaneous stimulation, it has a drawback: an external coil must be worn to deliver power. Arm rehabilitation participants reported this as an encumbrance, preferring a system that includes no worn devices. For an intermittent use therapeutic device as used in the arm rehabilitation study, the coils are inconvenient but useful and worthwhile. Development of battery-powered implants will allow a stimulator to operate without the bulky external coils. The RFM system described for poststroke arm rehabilitation has demonstrated the feasibility of, and confirmed the need for, a closed-loop, minimally invasive, fully implantable distributed neurostimulator system. The Alfred Mann Foundation is currently developing the Functional Electrical Stimulation Battery-Powered Microstimulator (FEBPM) to fulfill this need. This next-generation microstimulator is powered by a rechargeable lithium-ion battery within each implantable device, and receives commands from a remote master control unit (MCU) by wireless radio frequency communication. The system architecture allows the MCU to communicate with over 800 implanted devices. The FEBPM system is designed to deliver synchronized stimulation by multiple devices, allowing coordination of function. The implant device is approximately 3.6mm in diameter and 27.5mm long, and is implanted using a minimally invasive procedure. Charging of the implant battery(ies) occurs on an intermittent basis using a non-invasive system that is capable of charging multiple devices simultaneously. FEBPM system components are illustrated in Figure 4. We expect that this device will allow superior performance and patient compliance, with the externally worn devices of the RFM system no longer required.

image

Figure 4.  Functional electrical stimulation battery-powered microstimulator (FEBPM) system components. The master control unit (MCU) communicates wirelessly with multiple implanted devices, and with the charge controller. The charge controller is used intermittently to drive a charging coil, which can charge multiple implanted devices simultaneously. The MCU interfaces by ethernet connection to either a clinician’s fitting system, or the patient interface.

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Conclusions

  1. Top of page
  2. Abstract
  3. Electrical Stimulation in CP
  4. Review of the literature
  5. Common Themes and Limitations of Prior Studies
  6. The Need for Better Devices and the Implanted Microstimulator
  7. Arm Rehabilitation Study
  8. Features for an Electrical Stimulation System in CP
  9. Development of an Implanted Battery-Powered Microstimulator
  10. Conclusions
  11. References

The primary literature on use of ES in CP is dominated by case studies and uncontrolled studies, and suffers from a lack of standards. Nonetheless, results of these studies demonstrate reasons to be optimistic that ES holds promise for therapeutic value. A confounding factor is that most studies have used surface stimulation, which suffers from non-selectivity and the potential inability to use proper dosing because of collateral stimulation of pain receptors. The use of long-term implantable stimulation devices should be pursued. The Alfred Mann Foundation has developed an implantable RFM and has demonstrated this device in feasibility studies. We are currently developing the FEBPM, which may well serve the needs of the CP population.

References

  1. Top of page
  2. Abstract
  3. Electrical Stimulation in CP
  4. Review of the literature
  5. Common Themes and Limitations of Prior Studies
  6. The Need for Better Devices and the Implanted Microstimulator
  7. Arm Rehabilitation Study
  8. Features for an Electrical Stimulation System in CP
  9. Development of an Implanted Battery-Powered Microstimulator
  10. Conclusions
  11. References
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