Non-invasive spinal cord stimulation for spasticity control and augmentation of motor control in spinal cord injured individuals

Abstract

Altered brain control over the spinal cord following a spinal cord injury (SCI) is clinically manifested as paralysis or paresis below the lesion as well as spasticity, one of the most disabling secondary sequelae (1). A neuromodulative approach for the treatment of upper motor neuron disorders is electrical spinal cord stimulation (SCS) via epidurally placed implants (2, 3). When specifically targeting the lumbosacral spinal cord, a variety of effects can be induced by epidural SCS in the paralyzed legs of severely spinal cord injured (SCI) individuals, depending on the applied stimulation parameters. These effects range from the alleviation of spinal spasticity at stimulation frequencies of 50-100 Hz (4) to the generation of coordinated multi-joint flexion-extension movements at 20-50 Hz (5-7) and bilateral extension of the lower limbs at 5-15 Hz (8). Further, when applied in combination with assisted, body-weight supported treadmill stepping, epidural SCS can augment the lower-limb motor activities produced in persons with motor-incomplete (9, 10) and -complete SCI (11-13). With the development of a skin-electrode based version of SCS (14, 15), a method became available to non-invasively depolarize (at least a subset of) the input structures to the lumbosacral spinal circuitry activated by the epidural technique, i.e., large-diameter afferent fibres of the L2-S2 posterior roots (16, 17). These similarities in the direct effects of epidural and transcutaneous SCS led us to assume that the latter may serve as a non-invasive, costeffective alternative to alleviate spinal spasticity and facilitate residual motor control, as well as to augment rhythmic motor outputs produced during (assisted) treadmill stepping in individuals with SCI of different severity. Here, we report on preliminary findings of transcutaneous SCS-induced neuromodulative effects. Transcutaneous SCS for spasticity control and facilitation of residual motor control. A single 30-minute application of transcutaneous SCS in a relaxed supine position with a frequency of 50 Hz and an intensity below motor threshold for the lower limb muscles temporarily alleviated spinal spasticity and facilitated voluntary movements in three individuals with chronic, motor-incomplete SCI (18). Specifically, increased muscle tone, excessive withdrawal responses as well as clonus-like muscle activity were distinctly reduced after the stimulation. Functionally, two of the three subjects tested increased their walking speed in the 10-meter walk test by 32% on average. The anti-spastic carry-over effects were subjectively reported to have persisted for two to six hours after the stimulation. In an additional motor-incomplete SCI subject, we tested potential summation effects of transcutaneous SCS when applied five times a week over a period of six weeks (19). We found that the stimulation induced anti-spastic effects as assessed by clinical and electrophysiological tests were progressively increasing over the course of time. After six weeks, the subject discontinued the stimulation, and persisting SCS-induced effects could still be detected one week later. Combined effects of transcutaneous SCS and (assisted) treadmill stepping. Transcutaneous lumbosacral SCS at 30 Hz with intensities below the lower-limb motor threshold modified the motor outputs to the leg muscles and the gait kinematics of three subjects with chronic, motor-incomplete SCI while stepping actively on a treadmill (20). The modifications occurred within physiologically appropriate phases of the gait cycle, despite the invariant stimulation parameters. Further, no electromyographic activities were produced in the lower-limb muscles by the stimulation alone, i.e., without the subjects´ voluntary attempt to step. We thus assume that the continuous, driving input provided by transcutaneous SCS elevated the physiological state of the lumbar locomotor circuits that in turn became more responsive to the supraspinal commands via the residual descending pathways. Further, in four subjects with motor-complete SCI, 30-Hz transcutaneous SCS applied at above-motor threshold level considerably increased the number of lower-limb muscles responding to assisted treadmill stepping using a robotic-driven gait orthosis (Minassian et al., 2010). These interim findings suggest that transcutaneous SCS is a promising new strategy in the management of spinal spasticity and augmentation of motor control after SCI. Further studies should clarify the dependence of specific lesion profiles and different stimulation parameters on the achieved outcome. Eventually, testing different combinations of transcutaneous SCS with other treatment modalities shall further potentiate the obtainable therapeutic effects.

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