A Modular Approach to Retraining Muscles after Stroke - International

9th Annual Conference of the International FES Society September 2004 – Bournemouth, UK __________________________________________________________________________________________

A Modular Approach to Retraining Muscles after Stroke Richmond FJR 1, Baker LL 2,3, Winstein C 2, Waters RL 3, Loeb GE 1 1

AE Mann Institute for Biomedical Engineering, University of Southern California, Los Angeles,USA Dept. Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, USA 3 Rancho Los Amigos National Rehabilitation Center, Downey, CA, USA 2

Email: [email protected] ; Website: http://ami.usc.edu

Abstract The pathophysiology, clinical course and residual disability of patients presenting with a hemiparetic stroke are highly variable. This makes it difficult to apply a highly specific treatment modality to a large population of patients and even more difficult to identify its safety and efficacy vis-à-vis the incremental and ad hoc application of myriad conventional treatments. We are conducting a set of clinical trials of a new class of modular injectable microstimulators that can be used in a wide variety of sites and exercise paradigms. Initial results from electrically induced exercise of the shoulder and wrist and finger muscles are encouraging. Actual clinical experience suggests, however, that the real power of such treatment resides in its ability to be adapted to the limitations, needs and progress of each patient and to complement other treatments rather than adhering slavishly to research protocols.

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Introduction

The clinical disorder known as stroke covers a wide range of pathophysiology and clinical disability. The branching pattern of the vasculature varies from patient to patient and the premorbid capabilities and representation of a given sensory or motor function depends on the history of each individual. The amount of brain tissue that is permanently lost as opposed to temporarily nonfunctional depends on the extent of the obstruction as well as the availability and development of collateral circulation. The resulting heterogeneity of symptoms makes it difficult to apply and assess therapeutic interventions. When physical therapists devise treatments to rehabilitate stroke patients, they proceed incrementally based on the history, current condition and needs of the individual patient. Spontaneous changes in the condition of the patient (for better or worse) may make a given treatment inappropriate, or may require different or supplemental modalities, particularly in the early stages of recovery.

Postponing treatment until the patient is “stable” is likely to make recovery more difficult (see below). These circumstances are anathema to the usual design of a clinical trial intended to demonstrate efficacy of a specific treatment. One physiological consequence of a paretic limb is actually quite predictable and amenable to treatment by neuromuscular electrical stimulation (NMES). This is the disuse atrophy and consequent weakness and fatigability of the paretic muscles. Disuse atrophy develops rapidly. Thus, it tends to interfere with any spontaneous recovery of function as motor function of the cortex improves. Disuse atrophy leads to a variety of sequelae (e.g. shoulder subluxation [1] and spasticity (e.g. flexion contractures of the hand). These secondary problems further compromise the ability of the patient to participate in and benefit from physical therapy such as constraint induced therapy, robotically assisted therapy, and other techniques that might encourage relearning to use the paretic limb. Even modest amounts of daily NMES can substantially prevent or reverse disuse atrophy [2], but it is used relatively infrequently in most clinics and prescribed rarely for home use. The available technology of transcutaneous electrodes requires careful placement and adjustment, which many patients and their caregivers find difficult to master. Unpleasant sensations and skin irritation may result when relatively large currents are applied to the skin. Surgically implanted electrical stimulators can overcome these problems in principle, but they are typically expensive, bulky and difficult to adapt to changing rehabilitative needs.

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Methods

BION™ wireless microstimulators provide useful features for the stimulation of paretic muscles. One of more BIONs can be injected into various muscles or near muscle nerves to provide precise and selective control of the intensity and temporal patterning of individual muscle activation. Each device receives power and its own unique command signals from an externally worn RF transmission coil [3]. Additional BIONs can be injected at any time


in a simple outpatient procedure. They are inert and biocompatible, so may be left in place indefinitely whether or not they are being used by the patient. After implantation, the clinician determines the threshold to produce a visible twitch of each muscle and designs one or more exercise programs consisting of trains of electrical pulses at a desired rate (1-50pps) and intensity (specified as a multiple of threshold stimulus charge, by controlling the pulse current over the range 0-30mA and pulse duration over the range 2-512µs). The onset, duration and interleaving of pulse trains from various implants are easily set using a graphical interface on a portable personal computer (ClinFit™). The exercise programs are downloaded into a portable, microprocessorbased controller (Personal Trainer™) that provides the patient with start/stop controls and records their usage. The externally worn coils come in several shapes to match various implantation sites.

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Clinical Studies

We are conducting several clinical studies that target weakness of the arm and hand. Because of regulatory considerations, each study deals with a different clinical problem and tests the safety and efficacy of a specific NMES intervention against various control treatments, as summarized below: 3.1 Prevention of shoulder subluxation in subacute stroke patients The methods and results of the first ten patients enrolled in this prospectively randomized control and cross-over study have been published [4]. The center continues to accrue patients at a low rate. Briefly, patients with a flaccid arm at 4-10 weeks post-stroke who are otherwise mentally intact are implanted with one BION in each of the supraspinatus and middle deltoid muscles. They self-administer exercise programs for 20-30 minutes, 2-3 times per day. The programs are designed to produce maximal recruitment of the implanted muscles at low stimulus rates (typically 5 pps) in interrupted trains (typically 3s on and 3s off) that produce relatively low forces and little arm movement. Most patients were already clinically subluxed at the start of treatment; subluxation was substantially reduced or eliminated after a few weeks of stimulation. Pain is not well correlated with subluxation in timing or intensity but is known to develop eventually in 60-80% of such patients with conservative treatment. None of our initial 10 patients developed shoulder pain (2-4 year follow-up available on most).

The anecdotal findings may be even more revealing than the formal hypothesis, which had already been proven using surface stimulation [1]. The implanted patients all liked the sensations associated with muscle stimulation and most elected to continue self-administering the exercise after the end of the formal study period, whether or not their subluxation tended to recur. Muscles were strikingly weak and fatigueable at the start of stimulation but improved greatly within the first week or two. Some patients regained substantial voluntary control over shoulder abduction and elevation (the function of the stimulated muscles) even while the rest of their arm remained paralyzed. In one patient, such movement was functionally useful because he could place his hand on a pole which could then be grasped by using flexion tone, in order to help support himself when standing. 3.2 Reversal of shoulder subluxation in chronic stroke patients BION treatment similar to the subacute study described above is currently being applied to patients with stable, chronic shoulder subluxation (>6 mo post-stroke) and compared to surface stimulation in a cross-over study design. Implantation of the correct sites is more difficult in chronic patients because of the more severe atrophy. Two of the first three BION patients have done better with surface stimulation; one achieved complete reduction with BION stimulation, which relapsed when stimulation was stopped. Three of four patients started on surface stimulation have expressed a strong desire to receive BION implants. Initial use of surface stimulation may be an effective way to identify patients whose symptoms are likely to respond to muscle exercise and to condition their muscles to facilitate BION injection. 3.3 Prevention and/or reversal of flexion contractures of the hand and fingers in chronic stroke patients Patients with paralyzed extensor muscles of the wrist and fingers usually develop permanent contractures because of the greater strength and spastic tone of the flexor muscles. Such contractures prevent even passive use of the hand. They are unsightly and, in the extreme, result in skin care problems when the fingernails press into the palm. The first three patients in this study constitute a pilot group intended to identify appropriate implantation sites for BIONs to produce balanced contraction of the various wrist and finger extensor muscles. The motor branching pattern of the


radial nerve suggests that multiple synergists can be recruited from individual sites, but there is substantial individual variability and disuse atrophy complicates assessment during implantation. All three chronic stroke patients implanted with BIONs obtained rapid and substantial reduction of their contractures. The stimulated muscles had rapid improvement in strength and fatigability, similar to that seen in shoulder patients. Unexpectedly, two patients progressed from minimal to substantial voluntary wrist extension, but did not achieve significant voluntary finger extension. 3.4 Retraining of voluntary extensor function in the hand and fingers of chronic stroke patients One of our team (CW) leads a research program to assess the efficacy of constraint induced therapy (CIT), that combines intensive taskspecific practice with encouraged use of the paretic limb by restraining the intact limb during activities of daily living [5]. The rationale is that the forced use stimulates cortical plasticity, permitting residual pyramidal tract pathways to take over some of the lost functions. Patients need to have at least some voluntary extensor function to be able to participate in the therapy, so it is not clear how much of any clinical improvement arises from changes in the descending control as opposed to improvements in muscle strength and fatigueresistance as a result of simple exercise. Furthermore, these effects are likely to be synergistic, with improved strength and functionality providing positive feedback that encourages more ambitious voluntary use of the hand. We have modified the BION Personal Trainer to trigger stimulation by using myoelectric activity from wrist extensor muscles recorded via surface electrodes. In an initial pilot study, even patients with insufficient wrist movement to qualify for CIT were able to produce EMG signals sufficient for triggering. However, the results of the flexion contracture study suggest that simple electrically induced exercise of the wrist extensor muscles can rapidly advance their voluntary function even beyond the eligibility requirements for CIT; recovery of finger function may be a better goal for CIT or triggered stimulation. This has motivated us to design the pending study with a more complex, four-arm cross-over design that will provide comparisons of automatic BION exercise vs. myoelectrically initiated BION exercise vs. CIT vs. conservative treatment, as well as different

combinations treatments.

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and

sequences

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Discussion and Conclusions

A stroke patient might well qualify for or benefit from two or more of the above BION treatments, as well as from others, to deal with atrophy and paresis in both the arm and the leg. The rate and ordering of treatments and the benefits achieved thereby are likely to vary substantially from patient to patient, in ways that are not predictable at the outset but become readily apparent to a therapist in the course of each treatment. Success in activities of daily living usually depends synergistically on a spectrum of capabilities of many neural and musculoskeletal components. It seems likely that the power of BION treatment will stem not from its ability to replace the therapist but to provide a flexible new tool to reverse disuse atrophy and to motivate and empower patients to benefit from more aggressive physical therapy. References [1]

[2]

[3]

[4]

[5]

Faghri, P. D., Rodgers, M. M., Glaser, R. M. et al., "The effects of functional electrical stimulation on shoulder subluxation, arm function recovery, and shoulder pain in hemiplegic stroke patients," Arch.Phys.Med.Rehabil., vol. 75, pp. 73-79, 1994. Baker, L. L., Wederich, C. L., McNeal, D. R. et al., NeuroMuscular Electrical Stimulation, 4th ed. Downey, CA: Los Amigos Research & Education Institute, Inc., 2000. Cameron, T., Loeb, G. E., Peck, R. et al., "Micromodular implants to provide electrical stimulation of paralyzed muscles and limbs," IEEE Trans.Biomed.Eng, vol. 44, no. 9, pp. 781-790, 1997. Dupont, A. C., Bagg, S. D., Creasy, J. L., et al., "First patients with BION(R) implants for therapeutic electrical stimulation," Neuromodulation, vol. 7 pp. 38-47, 2004. Winstein, C. J., Miller, J. P., Blanton, S., et al., "Methods for a multisite randomized trial to investigate the effect of constraint-induced movement therapy in improving upper extremity function among adults recovering from a cerebrovascular stroke," Neurorehabil.Neural Repair, vol. 17, pp. 137152, 2003.

Acknowledgement Supported by NIH Bioengineering Research Partnership Grant #R01EB002094, the NSF Engineering Research Center for Biomimetic MicroElectronic Systems, and the A.E. Mann Institute.