Effects of Lumbosacral Spinal Cord Epidural Stimulation for Standing after Chronic Complete Paralysis in Humans

Enrico Rejc, Claudia Angeli, Susan Harkema, Enrico Rejc, Claudia Angeli, Susan Harkema

Abstract

Sensory and motor complete spinal cord injury (SCI) has been considered functionally complete resulting in permanent paralysis with no recovery of voluntary movement, standing or walking. Previous findings demonstrated that lumbosacral spinal cord epidural stimulation can activate the spinal neural networks in one individual with motor complete, but sensory incomplete SCI, who achieved full body weight-bearing standing with independent knee extension, minimal self-assistance for balance and minimal external assistance for facilitating hip extension. In this study, we showed that two clinically sensory and motor complete participants were able to stand over-ground bearing full body-weight without any external assistance, using their hands to assist balance. The two clinically motor complete, but sensory incomplete participants also used minimal external assistance for hip extension. Standing with the least amount of assistance was achieved with individual-specific stimulation parameters, which promoted overall continuous EMG patterns in the lower limbs' muscles. Stimulation parameters optimized for one individual resulted in poor standing and additional need of external assistance for hip and knee extension in the other participants. During sitting, little or negligible EMG activity of lower limb muscles was induced by epidural stimulation, showing that the weight-bearing related sensory information was needed to generate sufficient EMG patterns to effectively support full weight-bearing standing. In general, electrode configurations with cathodes selected in the caudal region of the array at relatively higher frequencies (25-60 Hz) resulted in the more effective EMG patterns for standing. These results show that human spinal circuitry can generate motor patterns effective for standing in the absence of functional supraspinal connections; however the appropriate selection of stimulation parameters is critical.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. EMG and ground reaction forces…
Fig 1. EMG and ground reaction forces recorded during full weight-bearing standing.
Time course of EMG and ground reaction force recorded during representative standing without stimulation and with stimulation parameters that promoted standing with the least amount of assistance. Participants A45 and A53 were able to stand placing their hands on the horizontal bars of the standing apparatus to assist balance. Participants B07 and B13 also used elastic cords fixed to the apparatus to assist with hip extension (S1 Video). Stimulation frequency, amplitude and electrode configuration (cathodes in black, anodes in grey, and non-active in white) are reported for each participant. Participant A53 was stimulated with four programs (P.1 to P.4) delivered sequentially at 10 Hz, resulting in an ongoing 40 Hz stimulation frequency. IL: iliopsoas; GL: gluteus maximus; MH: medial hamstring; VL: vastus lateralis; TA: tibialis anterior; MG: medial gastrocnemius; SOL: soleus.
Fig 2. EMG and ground reaction forces…
Fig 2. EMG and ground reaction forces during sitting to standing transition.
Time course of EMG and ground reaction force recorded during sitting to standing transition from participants A45 (Panel A) and A53 (Panel B). Panels C and D: Spinal cord evoked responses taken from the windows entered in A and B, respectively (left window: sitting; right window: standing). The black trace is the average of 15 spinal cord evoked potentials represented in grey. Vertical grey dotted line: stimulation onset. Stimulation frequency, amplitude and electrode configuration (cathodes in black, anodes in grey, and non-active in white) are reported. Participant A53 was stimulated with four programs (P.1 to P.4) delivered sequentially at 10 Hz, resulting in an ongoing 40 Hz stimulation frequency. IL: iliopsoas; GL: gluteus maximus; MH: medial hamstring; RF: rectus femoris; VL: vastus lateralis; TA: tibialis anterior; MG: medial gastrocnemius; SOL: soleus.
Fig 3. EMG and ground reaction forces…
Fig 3. EMG and ground reaction forces recorded during standing with stimulation parameters optimal for other individuals.
Time course of EMG and ground reaction force recorded from participants B07 (Panels A and B) and B13 (Panels C and D) during standing with stimulation frequency and electrode configuration optimal for other participants: A, specific for B13; B and D: specific for A45; C: specific for B07. Stimulation amplitude was adjusted to optimize standing. External assistance to maintain hip and knee extension was needed to stand in all four conditions. IL: iliopsoas; GL: gluteus maximus; MH: medial hamstring; VL: vastus lateralis; TA: tibialis anterior; SOL: soleus.
Fig 4. EMG and ground reaction forces…
Fig 4. EMG and ground reaction forces recorded during standing with different electrode configurations.
EMG and ground reaction force were recorded from all participants during standing. Stimulation amplitude and frequency (3.0 V and 25 Hz, respectively) were delivered with a wide-field electrode configuration. Cathodes were placed either in the caudal (Panel A) or rostral (Panel B) portion of the array; anodes were placed specular to cathodes, as shown in the bottom left of the figure.Panel C: Average (N = 100) peak to peak spinal cord evoked potentials amplitude recorded from the four participants during standing with cathodes placed caudally (black bars, Configuration A) or rostrally (white bars, Configuration B). As for participant B13, spinal cord evoked potentials were taken from the windows entered in A and B. TA: tibialis anterior; MG: medial gastrocnemius; SOL: soleus.
Fig 5. EMG and ground reaction force…
Fig 5. EMG and ground reaction force recorded during standing with different stimulation amplitudes.
EMG and ground reaction force recorded from participant A53 during standing with three different stimulation amplitudes (1.0, 3.0 and 5.0 V) delivered at either 25 Hz or 50 Hz. Electrode configuration (cathodes in black, anodes in grey, and non-active in white) is reported. MH: medial hamstring; VL: vastus lateralis; TA: tibialis anterior; SOL: soleus.
Fig 6. EMG recorded during standing at…
Fig 6. EMG recorded during standing at lower and higher stimulation frequency.
Panel A: Continuous EMG pattern recorded from participant A53 during standing at lower (5 Hz) and higher (30 Hz) stimulation frequency. Panel B: Spinal cord evoked responses taken from the windows entered in A. The black trace is the average of 20 responses represented in grey. Vertical grey dotted line: stimulation onset. Panel C: Coefficient of variation (CV) calculated from the spinal cord evoked responses reported in B (black line: 5 Hz; grey line: 30 Hz). Stimulation amplitude and electrode configuration (cathodes in black, anodes in grey, and non-active in white) are reported. MH: medial hamstring; VL: vastus lateralis; SOL: soleus.

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