Implantable Spinal Cord Stimulation and Walking
Discussion
Because implantable spinal cord stimulation, like epidural spinal cord stimulation (ESCS) and laparoscopic implantation of neuroprosthesis (LION), require surgery so there are no RCT studies in this area and the case series studies samples are small.
Wagner et al. (2018) included three males with chronic SCI who displayed severe lower limb deficits or complete paralysis that prevented them from walking overground; they implanted a pulse generator into all three participants to deliver spatially selective stimulation to the lumbosacral spinal cord with timing that coincided with the intended movement. After the implantation, the three participants received a rehabilitation program focused on walking on a treadmill and over ground, complemented with muscle strengthening and standing training (Wagner et al. 2018). In one week, spatiotemporal stimulation enabled all participants to walk overground (using the gravity assist) voluntarily while the stimulation was on, covering distances as long as 1.0 km without showing muscle exhaustion or gait impairments (Wagner et al. 2018). After a few months, rehabilitation promoted neurological recovery that translated into improvements in WISCI, in 6MWT, in 10MWT, or LEMS without stimulation; and they could even walk or cycle in ecological settings during spatiotemporal stimulation (Wagner et al. 2018).
In 2022, as part of the ongoing clinical trial ‘Stimulation Movement Overground’ (STIMO) (www.clinicaltrials.govidentifier NCT02936453), two pre-post studies were published (Kathe et al. 2022; Rowald et al. 2022). Kathe et al. (2022) included nine participants with chronic and severe or complete motor paralysis. Participants, after receiving spatiotemporal ESCS plus LT, showed that compared to before the training program, LEMS and walking distance (6MWT) were significantly improved (Kathe et al. 2022). Moreover, weight-bearing capacities improved considerably over time, which enabled the participants to walk outdoors with ESCS on and an assistive device for stability (Kathe et al. 2022). It should be noted that participants who exhibited residual function before training displayed a pronounced increase in lower limb motor scores that restored walking, even in the absence of ESCS in four participants (Kathe et al. 2022). This sustained recovery suggested that the stimulation triggered the remodeling of the spinal neurons to bring the locomotion network back online (Lewis 2022). Interestingly, when ESCS was active, nerve-cell activity at the site of stimulation decreased; and after further investigation, Kathe et al. (2022) discovered the neurons responsible for the rehabilitation enhancement and concluded that SCVsx2::Hoxa10 neurons located in the intermediate laminae of the lumbar spinal cord possess the anatomical and functional properties that are compatible with the key therapeutic features of ESCS rehabilitation.
Rowald et al. (2022) established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead, guided its neurosurgical positioning, and developed software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. Three participants with chronic and complete sensorimotor paralysis and unable to take any step followed a rehabilitation program (which comprised walking on a treadmill and overground with multiple assistive devices, sit-to-stand, standing, leg and trunk muscle exercises, swimming and cycling) with this computational ESCS framework and software four to five times per week for five months (Rowald et al. 2022). Immediate recovery of walking was shown; on the first day, all three participants could step independently on a treadmill with BWS, and after 1–3 additional days, gait patterns were sufficiently optimized to enable the three participants to ambulate independently overground with BWS (Rowald et al. 2022). All three participants progressively regained full weight-bearing capacities, which translated into the ability to stand, walk, cycle, swim and control trunk movements in community settings (Rowald et al. 2022). Lastly, Rowald et al. (2022) showed that these improvements coincided with a substantial increase in the mass of leg and trunk muscles; moreover, two of the participants recovered the ability to activate proximal muscles voluntarily without ESCS, indicating neuroplastic recovery. These promising effects of different procedures of ESCS, should be confirmed with larger trials, which at time of writing, are currently underway (‘Stimulation Movement Overground’ (STIMO) (www.clinicaltrials.govidentifier NCT02936453).
The laparoscopic implantation of neuroprosthesis (LION) procedure has shown early and long-term effects in pre-post studies for regaining motor and sensory function in patients with paraplegia after SCI (Possover 2014; Possover 2021). In an RCT, Kasch et al. (2022) compared 16 participants with chronic complete (AIS A) SCI receiving the LION procedure were randomly allocated to subsequent neurostimulation and training or long-term home-based NMES for the gluteal and the quadriceps muscle groups (Kasch et al. 2022). At one-year follow-up, between-group comparisons in WISCI II scores were significant, as there was an increase from 0 to 1 in 5 of 8 participants in the LION Group, whereas there was no change in the control group participants (Kasch et al. 2022). More recently, a case series study by Lemos et al. (2023) included 30 patients with chronic and complete SCI who had received the LION surgical procedure and an intensive rehabilitation protocol to learn how to use the movements generated by the neuromodulator to enhance their rehabilitation and ADLs. At one year follow-up, median WISCI II score significantly improved from a median of 0 to median of 5. In addition, 18 of 25 (72%) patients with thoracic injury and three of five (60%) patients with cervical injury managed to establish independent walker-assisted gait (WISCI II score ≥ 7), using only ankle-foot orthosis (AFO) to stabilize their ankles (Lemos et al. 2023).
It should be noted that the majority of studies with patients who received ESCS did not report if there were any AEs (Wagner et al. 2018; Rowald et al. 2022; Kathe et al. 2022). Kasch et al. (2022) reported that in one participant, the implantable pulse generator in the LION procedure migrated within two months after the operation, although after the reposition during an outpatient clinic operative procedure, the implantable pulse generator was fully functioning and the training program was resumed. Lemos et al. (2023) and Possover (2021) registered no intraoperative complications, but the most frequent post-operative complication was electrode displacement (which occurred in situations where the movements that should be avoided were inadvertently performed), which happened in three (10%) cases and required a reintervention for electrode repositioning. Another complication observed by Lemos et al. (2023) and Possover (2021) was one case (3.3%) of infection of the neuromodulator, and after several antibiotic courses attempted with no success, the neuromodulator was removed at five months postoperatively with no further complications. However, it should be noted that no discomfort or pain was reported by any patient, and no episodes of dysreflexia were observed as a result of nerve stimulation (Lemos et al. 2023).
Rademeyer et al. (2021) conducted a scoping review to synthesize the effects of ESCS on function in people living with SCI. From a total of 48 studies including 373 participants, 27.1% (n = 13) revealed promising (but preliminary) findings on lower extremity function (i.e., standing or locomotion) (Rademeyer et al. 2021). It was revealed that the epidural space posterior to the spinal cord was the optimal stimulation site to enable positive effects on lower extremity functional goals, with L2 as the preeminent level to stimulate locomotion and stimulation parameters being individually optimized often based on sensory and motor thresholds (Rademeyer et al. 2021). It was stated that ESCS may be combined with movement training (BWSTT, OGT or EAW) (Rademeyer et al. 2021).
Conclusions
There is level 2 evidence (from 1 RCT: Kasch et al. 2022) and level 4 evidence (from 1 case series and 1 pre-post study: Lemos et al. 2023; Possover 2021) that the LION procedure for bilateral neuromodulation of femoral, sciatic, and pudendal nerves followed by an intensive rehabilitation protocol; despite very few cases of complications (electrode displacement and infection of the neuromodulator); provides long-term beneficial effect on walking ability (WISCI II) in patients with chronic and complete SCI.
There is level 4 evidence (from 3 pre-post studies: Kathe et al. 2022; Rowald et al. 2022; Wagner et al. 2018) that ESCS (regardless of the process used) and a subsequent training program based on LT is relatively safe and provides improvements in walking capacity, LEMS, and independence in ADLs in patients with chronic SCI and complete or severe motor paralysis.
