ABSTRACT
Preliminary results are summarized from two ongoing clinical trials of
injectable microstimulators used to provide therapeutic exercise to weak or
paralyzed muscles. The first trial is
aimed at preventing chronic shoulder subluxation
after stroke by stimulating deltoid and supraspinatus muscles daily for six
weeks. Results of five subjects showed reductions of shoulder subluxation only
for experimental subjects and muscle thickness increases in stimulated
muscles. The second trial is aimed at
strengthening the quadriceps muscles in patients with chronic osteoarthritis of
the knee. Three subjects have been
recruited. Results from the first
subject indicate that stimulation increased muscle thickness and improved knee
function.
BACKGROUND
BIONs are microminiature, single channel stimulators that can be injected into muscles. They receive power and individually addressable commands from an external magnetic field. They have been shown to be safe and effective for stimulating muscles in animals[1,2] and reducing atrophy in paralyzed rat muscles[3]. They offer a low-risk, reliable and cost-effective technology for delivering therapeutic electrical stimulation that can be self-administered by the patient.
Shoulder subluxation is often observed in patients who have suffered a stroke. It is often painful and can lead to the complete disuse of the affected arm[4]. A few studies have shown that shoulder subluxation can be reversed over 6 weeks with daily electrical stimulation of the deltoid and supraspinatus muscles, but they have used long sessions of stimulation (4-7h/d) and less convenient technologies such as transcutaneous or percutaneous electrodes[5,6,7].
Osteoarthritis of the knee is a disease found in approximately one third of the population over 65[8]. It is accompanied by pain and reduced function of the knee as well as reduced mass and strength of thigh muscles. Strengthening of the quadriceps muscles can reduce joint pathology[9] but many patients have difficulty achieving a sufficient intensity and/or duration of voluntary exercise.
RESEARCH QUESTION
To determine whether electrical stimulation delivered by BIONs is safe and effective for exercising muscles, increasing their thickness and decreasing joint pathology when applied in an easily tolerated schedule of intermittent, low frequency contractions totaling ~1h/d in 2-3 sessions.
METHOD
For the shoulder study, hemiplegic patients 3-10 weeks post stroke are randomized into a treatment group who begin regular exercise with BIONs (one implanted in middle deltoid and one in supraspinatus muscles) or a control group, who are treated conservatively. After 6 weeks, the stimulated group stops using the BIONs for 6 weeks and the control group is offered BION implants if they have become symptomatic.
For the knee study, patients with chronic osteoarthritis are observed for 12 weeks to determine their baseline state. They are then implanted with BIONs near the common femoral nerve and in the vastus medialis muscle, which are used to exercise the quadriceps muscles for 12 weeks. In both studies, therapy starts 4-7 days after implantation, and consists of 2-3 stimulation sessions of 10-30 minutes each day. The intensity and duration of stimulation is gradually increased as the patient’s fatigue resistance improves. Outcome measures include muscle thickness measured with ultrasound or MRI, strength and function testing, and radiographic assessment of the affected joint.
RESULTS
stim
All patients implanted with BIONs found the sensations associated with muscle
stimulation to be agreeable and they complied enthusiastically with the
prescribed treatment. There were no adverse
events or complications related to the implants or the exercise treatment. Stimulation thresholds were stable over time,
while the strength and fatigue-resistance of maximal contractions increased.
stim
Complete results from three
experimental and two control subjects in the shoulder study were available at
the end of 2000. The degree of subluxation of the experimental subjects after 6
weeks of therapy was estimated by the Dv index
compared with the control side, as shown in Fig. 1. Large reductions of subluxation were seen in
experimental patients 1 and 2 (-87 and -111%, respectively), but not in
experimental patient 4, who was stimulated only in the deltoid muscle, or in
either control patient. When stimulation
was discontinued (weeks 6-12), subluxation started to return in patient 1. Thickness of the stimulated muscles (measured
by ultrasound) typically was maintained or increased during the stimulation
period (p<0.05; Fig. 1), on average by 15% (range: -11 to 44%). Some of that effect carried over during the 6
weeks off therapy, possibly related to improved voluntary shoulder
abduction. In control subjects, muscle
thickness did not increase and often declined.
In the one subject with only deltoid stimulation, deltoid thickness
increased (2 to 11%, depending on location of measurement) but supraspinatus
thickness did not (-5 to 0%).
Some patients have elected to continue stimulation after the conclusion of the 12 week protocol. Patient 1 went back on stimulation and successfully resolved the subluxation that was reforming; he has now been using daily stimulation for over one year. Patient 2 also went back on stimulation because he had shoulder pain (but no objective subluxation); he discontinued stimulation after four weeks when the pain resolved. Control patient 5 developed subluxation and pain and elected to receive BION implants; symptoms improved after 8 weeks of stimulation.
In the study of osteoarthritis, three patients have been recruited; complete results from one are available. Knee function improved and pain decreased over the 12 weeks of stimulation (WOMAC index plotted in Fig. 2). Muscle thickness increased in rectus femoris in both the medio-lateral and in the antero-posterior planes by 15% on average (range 2-40%, depending on location of measurement) (p<0.00005). The second patient has been stimulated at the femoral nerve site only and has reported improved function and reduced pain after the first few weeks of stimulation.
DISCUSSION
The results from these clinical trials are preliminary but encouraging. We estimate that 10-20 patients will be needed in each study to demonstrate effectiveness clearly. Plans are underway for clinical trials in several other applications requiring chronic therapeutic exercise of atrophic muscles.
REFERENCES
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