Transcutaneous Spinal Neuromodulation Reorganizes Neural Networks in Patients with Cerebral Palsy

Abstract

Spinal neuromodulation and activity-based rehabilitation triggers neural network reorganization and enhances sensory-motor performances involving the lower limbs, the trunk, and the upper limbs. This study reports the acute effects of Transcutaneous Electrical Spinal Cord Neuromodulation (SCONE™, SpineX Inc.) on 12 individuals (ages 2 to 50) diagnosed with cerebral palsy (CP) with Gross Motor Function Classification Scale (GMFCS) levels ranging from I to V. Acute spinal neuromodulation improved the postural and locomotor abilities in 11 out of the 12 patients including the ability to generate bilateral weight bearing stepping in a 2-year-old (GMFCS level IV) who was unable to step. In addition, we observed independent head-control and weight bearing standing with stimulation in a 10-year-old and a 4-year old (GMFCS level V) who were unable to hold their head up or stand without support in the absence of stimulation. All patients significantly improved in coordination of flexor and extensor motor pools and inter and intralimb joint angles while stepping on a treadmill. While it is assumed that the etiologies of the disruptive functions of CP are associated with an injury to the supraspinal networks, these data are consistent with the hypothesis that spinal neuromodulation and functionally focused activity-based therapies can form a functionally improved chronic state of reorganization of the spinal-supraspinal connectivity. We further suggest that the level of reorganization of spinal-supraspinal connectivity with neuromodulation contributed to improved locomotion by improving the coordination patterns of flexor and extensor muscles by modulating the amplitude and firing patterns of EMG burst during stepping.

Conflict of interest statement

V.R.E, holds shareholder interest in NeuroRecovery Technologies and hold certain inventorship rights on intellectual property licensed by The Regents of the University of California to NeuroRecovery Technologies and its subsidiaries. V.R.E and PG holds shareholder interest in SpineX Inc. and hold certain inventorship rights on intellectual property licensed by The Regents of the University of California to SpineX Inc.

© 2021. The Author(s).

Figures

Fig. 1

Patient no. 1 (age 2) stepping on a treadmill without and with spinal neuromodulation. Note that the patient is unable to step with the stimulation off whereas he begins to step voluntarily once the stimulation is turned on

Fig. 2

Patient no. 2 (age 7) stepping on a treadmill without and with spinal stimulation

Fig. 3

A Mean ± SE (n = 9 patients) angular excursion of the hip and knee joints without and with stimulation. B Interlimb coordination has shown from a representative patient (P2, n = 15 step cycles) by the knee-knee joint angle plots and intralimb coordination shown by the hip-knee plots without and with stimulation. Note the shaded area represents the variation over the 15-step cycle. C Mean ± SE (n = 9) coefficient of correlation of the trajectories shown in B with respect to the mean trajectory. D Mean ± SE (n = 9) area under the curve calculated for the plot in B. E Joint probability density (JPD) distribution plot of filtered rectified EMG amplitudes of the TA vs the Sol muscles without and with stimulation derived from an average of 15 step cycles for a representative patient (P2). F Mean ± SE (n = 9) percent data points in Quadrants (1 + 3) and (2 + 4) without vs with stimulation and G the mean percent data points for each quadrant. *Statistically significant at P < 0.05

Fig. 4

Hypothetical schematic of the brain, spinal cord, and muscles in children with cerebral palsy without and with acute spinal neuromodulation. F flexor motor pool, E extensor motor pool. Note the symbolic reduced lesion size to reflect a lesser dysfunctional supraspinal impact during spinal neuromodulation