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U Hofstötter, K. Minassian, S. M. Danner, M. Krenn, B. Freundl, H. Binder, W. Mayr, F. Rattay, M. Dimitrijevic:
"Non-invasive spinal cord stimulation for spasticity control and augmentation of motor control in spinal cord injured individuals";
Vortrag: International Symposium on Spasticity and Neural Control of Movement with the 30th Dr. Janez Faganel Memorial Lecture, Ljubljana, Slovenia (eingeladen); 04.09.2014 - 06.09.2014; in: "International Symposium on Spasticity and Neural Control of Movement with the 30th Dr. Janez Faganel Memorial Lecture: Program and Proceedings", J. Zidar (Hrg.); Section for Clinical Neurophysiology of the Slovenian Medical Association, Ljubljana, Slovenia (2014), ISBN: 978-961-6956-04-8; S. 54 - 56.

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.

References
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15. Minassian K, Hofstoetter U, Rattay F. Transcutaneous lumbar posterior root stimulation for motor control studies and modification of motor activity after spinal cord injury. In: Dimitrijevic MR, Byron A, Vrbova G, McKay WB, editors. Restorative neurology of spinal cord injury. New York: Oxford University Press, 2011: 226-55.
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17. Ladenbauer J, Minassian K, Hofstoetter US, Dimitrijevic MR, Rattay F. Stimulation of the human lumbar spinal cord with implanted and surface electrodes: a computer simulation study. IEEE Trans Neural Syst Rehabil Eng 2010; 18 (6): 637-45.
18. Hofstoetter US, McKay WB, Tansey KE, Mayr W, Kern H, Minassian K. Modification of spasticity by transcutaneous spinal cord stimulation in individuals with incomplete spinal cord injury. J Spinal Cord Med 2014; 37 (2): 202-211.
19. Hofstoetter US, Krenn M, et al. Short- and long-term effects of intermittent transcutaneous spinal cord stimulation on spinal spasticity and residual motor control. Society for Neuroscience Abstract Viewer and Itinerary Planner 2014.
20. Hofstoetter US, Hofer C, Kern H, Danner SM, Mayr W, Dimitrijevic MR, et al. Effects of transcutaneous spinal cord stimulation on voluntary locomotor activity in an incomplete spinal cord injured individual. Biomed Tech (Berl). doi:pii: /j/bmte.2013.58.issue-s1-A/bmt-2013-4014/bmt-20134014.xml.10.1515/bmt-2013-4014.
21. Minassian K, Hofstoetter U, Tansey K, Rattay F, Mayr W, Dimitrijevic MR. Transcutaneous stimulation of the human lumbar spinal cord: Facilitating locomotor output in spinal cord injury. Program No. 286.19. Abstract Viewer/Itinerary Planner. San Diego, CA: Society for Neuroscience 2010. Available at http://movementrecovery.org/drupal7/node/40

Projektleitung Frank Rattay:
Life Sciences - Linking Research and Patients' Needs Augmentation of residual neural control by non-invasive spinal cord stimulation to modify spasticity in spinal cord injured people