Rob Summers, 25, in the harness that provides support while he receives electrical stimulation to his spinal cord. The experimental procedure has allowed Summers to stand and move his legs voluntarily. Credit: Rob Summers |
A
team of researchers from the University of California, Los Angeles
(UCLA), the California Institute of Technology (Caltech), and the
University of Louisville have used a stimulating electrode array to
assist a paralyzed man to stand, step on a treadmill with assistance,
and, over time, to regain voluntary movements of his limbs. The
electrical signals provided by the array, the researchers have found,
stimulate the spinal cord’s own neural network so that it can use the
sensory input derived from the legs to direct muscle and joint
movements.
Rather
than bypassing the man’s nervous system to directly stimulate the leg
muscles, this approach takes advantage of the inherent control circuitry
in the lower spinal cord (below the level of the injury) to control
standing and stepping motions.
The study is published in the British medical journal The Lancet.
More
than 5.6 million Americans live with some form of paralysis; of these,
1.3 million have had spinal-cord injuries, often resulting in complete
paralysis of the lower extremities, along with loss of bladder and bowel
control, sexual response, and other autonomous functions.
The
work originated with a series of animal experiments beginning in the
1980s by study coauthors V. Reggie Edgerton and Yury Gerasimenko of the
David Geffen School of Medicine at UCLA that ultimately showed that
animals with spinal-cord injuries could stand, balance, bear weight,
and take coordinated steps while being stimulated epidurally—that is,
in the space above the dura, the outermost of the three membranes that
cover the brain and spinal cord.
Starting
eight years ago, Joel Burdick, a professor of mechanical engineering
and bioengineering at Caltech, teamed with the Edgerton lab to study how
robotically guided physical therapy and pharmacology could be coupled
to better recover locomotion in animals with spinal-cord injuries.
Building
upon these studies and the earlier work of Edgerton and Gerasimenko,
Burdick and Yu-Chong Tai, a Caltech professor of electrical engineering
and mechanical engineering, introduced the concept of high-density
epidural spinal stimulation, which uses sheet-like arrays of numerous
electrodes to stimulate neurons. The goal of the system, Burdick says,
“is to stimulate the native standing and stepping control circuitry in
the lower spinal cord so as to coordinate sensory-motor activity and
partially replace the missing signals from above”—that is, from the
brain—”and shout ‘get going!’ to the nerves.”
To
test this concept, which was first explored in animal models, the team
used a commercially available electrode array, which is normally used to
treat back pain. While this commercial array does not have all of the
capabilities of the arrays tested so far in animals, it allowed the team
to test the viability of high-density epidural stimulation in humans.
The results, Burdick says, “far exceeded” the researchers’ expectations.
The
subject in the new work is a 25-year-old former athlete who was
completely paralyzed below the chest in a hit-and-run accident in July
2006. He suffered a complete motor injury at the C7/T1 level of the
spinal cord, but retained some sensation in his legs.
Before
being implanted with the epidural stimulating array, the patient
underwent 170 locomotor training sessions over a period of more than two
years at the Frazier Rehab Institute. In locomotor training, a
rehabilitative technique used on partially paralyzed patients, the body
of the patient is suspended in a harness over a moving treadmill while
trained therapists repeatedly help manipulate the legs in a repetitive
stepping motion.
Electrical leads implanted in the paraplegic patient. Credit: Medtronic, Inc. |
The
training had essentially no effect on this patient, confirming the
severity of his spinal injury. The training also established a
“baseline” against which the subsequent efficacy of the electrical
stimulation could be measured.
After
implantation with the device, however, the patient could—while
receiving electrical stimulation, and after a few weeks of locomotor
training—push himself into a standing position and bear weight on his
own. He can now remain standing, and bearing weight, for 20 minutes at a
time. With the aid of a harness support and some therapist assistance,
he can make repeated stepping motions on a treadmill. With repeated
daily training and electrical stimulation, the patient regained the
ability to voluntarily move his toes, ankles, knees, and hips on
command.
The patient has no voluntary control over his limbs when the stimulation is turned off.
In
addition, over time he experienced improvements in several types of
autonomic function, such as bladder and bowel control, as well as
temperature regulation—a “surprise” outcome, Burdick says, that, if
replicated in further studies, could substantially improve the lives of
patients with spinal-cord injuries.
These
autonomic functions began to return before there was any sign of
voluntary movement, which was first seen in the patient about seven
months after he began receiving epidural stimulation.
Adds
Burdick, “This may help bladder and bowel function even in patients who
don’t have the strength to undergo rigorous physical training like this
patient”—who was an athlete and was in comparatively excellent physical
condition before his injury.
The
scientists aren’t yet fully sure how these functions were regained—or,
indeed, how the control of voluntary function was returned through the
procedure. “Somehow, stimulation by the electrodes may have reactivated
connections that were dormant or stimulated the growth of new
connections,” Burdick says. Almost certainly, reorganization of the
neural pathways occurred below and perhaps also above the site of
injury.
Notably,
the patient had some sensation in his lower extremities after his
injury, which means that the spinal cord was not completely severed;
this may have affected the extent of his recovery.
Implanted electrode array. Credit: The Lancet |
The
Food and Drug Administration (FDA) gave the research team approval to
test five spinal-cord injury patients; the next patient will be matched
with the first, in terms of age, injury, and physical ability, to see if
the findings can be replicated. In subsequent trials, patients who have
no sensation will be implanted with the device, to see if this
influences the outcome.
“This is a significant breakthrough,” says Susan Harkema of University of Louisville, the lead author of the paper in The Lancet. “It opens up a huge potential to improve the daily functioning of individuals.”
“While these results are obviously encouraging, we need to be cautious, and there is much work to be done,” says Edgerton.
One of the biggest obstacles is that the electrode array implanted in the human patient is FDA-approved for back pain
only. The use of the FDA-approved device was meant “as a test to see if
our concepts would work, providing us with additional ammunition to
motivate the development of the arrays used in animal studies,” says
Burdick. The current FDA-approved arrays, he adds, have many
limitations, “hence, the further development of the arrays that have
currently only been tested in animals should provide even better human
results in the future.”
Using
a combination of experimentation, computational models of the array and
spinal cord, and machine-learning algorithms, Burdick and his
colleagues are now trying to optimize the stimulation pattern to achieve
the best effects, and to improve the design of the electrode array.
Further advances in the technology should lead to better control of the
stepping and standing processes.
In
addition, he says, “our team is looking at other ways to apply the
technology. We may move the array up higher on the spinal column to see
if it could affect arms and hands, as well as the legs.”
Burdick
and his UCLA and University of Louisville colleagues hope that one day,
some individuals with complete spinal-cord injuries will be able to use
a portable stimulation unit and, with the assistance of a walker, stand
independently, maintain balance, and perform some effective stepping.
In addition, says Burdick, “our team believes that the protocol might
prove useful in the treatment of stroke, Parkinson’s, and other
disorders affecting motor function.”
The
research in the paper, “Epidural stimulation of the lumbosacral spinal
cord enables voluntary movement, standing, and assisted stepping in a
paraplegic human,” was funded by the National Institutes of Health with
additional support provided by the Christopher and Dana Reeve
Foundation.
