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. 2020 Aug 27;37(18):1933–1953. doi: 10.1089/neu.2020.7033

Appendix Table A1.

Overview of the Use of Electrical Simulation following Spinal Cord Injury

Study Animal and injury model Electrical stimulation model Parameters Experimental groups Outcome (histological and behavioral)
Borgens, Roederer and Cohen (1981) -Model: ammocoete larva of the lampre, transection model of injury -5-6 days -Intensity: 10uA, constant current
-Electrode: saline bridge as wick electrode across the transected spinal cord
-ES with transection (n = 11)
-Sham ES and transection (n = 13)
-Electrophysiological: Action potentials (APs) conducted in both directions across lesion in ES group, no APs in sham group
-Histological: active growth in and across the lesion more common in ES-treated group
Borgens, Blight et al. (1986) -Model: Hartley female guinea pigs
-Injury: Low-thoracic dorsal transection
-Implanted direct current (DC) ES (epidural) across the SCI for mean 51 days -Power supply: DC, 9V (3x3V in series) LiMn battery
-Electrodes: Ag/AgCl on either side of the SCI
-ES: 1uA (n = 4)
-ES: 5uA (n = 6)
-ES: 10uA (n = 11)
-Sham ES (n = 11)
-Histological: ES showed more regeneration into scar; 10uA group extended into spinal cord below the lesion
Wallace, Tator et al. (1987) -Model: Wistar female rats
-Injury: T6-7 extradural clip compression (125g for 1min)
-Implanted continuous DC ES (epidural) across the SCI for 15-20 weeks -Voltage applied: <340mV (minimum for muscle twitch)
-Electromagnetic field: 460kHz
-Power supply: DC 9V ES group
-Frequency: 10Hz
-Electrodes: Pt on each side of the SCI (cathode proximal and anode distal)
-Sham ES with SCI (n = 10)
-ES with SCI: <340mV (n = 10)
-Behavioural:
1. Inclined plane: no difference between groups
-Neurophysiological: no difference between groups
-Histological: no difference in regeneration, scarring, or lesions between groups
-Adverse Events: 9/20 with single electrode dislodgement; 6/20 both electrodes dislodged; no changes in EM field based on position/location of rat
Maiman, Myklebust et al. (1987) -Model: cats
-Injury: T8 contusion with 20g weight drop from 25cm
-Intermittent (i.e., not continuous) DC ES monopolar below and bipolar (epidural) across the SCI, 3-5 months post-SCI examining effects on spasticity -Intensity: <1.0mA
-Frequency: 100Hz for 25ms
-Electrodes: Pt
-Multiple trials in same experiment (n = 14):
-Monopolar ES 100Hz for 25ms with negative electrode below SCI
-Monopolar ES 25Hz for 25ms with negative electrode below SCI
-Bipolar ES 100Hz for 25ms with negative electrode below SCI
-Behavioural: 100Hz group had less intense spasms than 25Hx group; Bipolar ES across SCI less effective than monopolar ES
-Histological: gliosis and cyst formation at SCI site in all groups, with no changes with electrode use
Politis and Zanakis (1988) -Model: Wistar female rats
-Injury: T8 contusion with 350g weight drop from 1cm against ventral plate
-Implanted continuous DC ES (epidural) across the SCI for 3 weeks -Intensity: 3uA
-Power supply: 1.5V zinc/alkaline/silver oxide battery
-Electrodes: 90/10 Pt:Ir attached to epidural pad
-SCI only (n = 6)
-No ES or SCI (normal) (n = 4)
-ES with SCI anode rostral (n = 6)
-ES with SCI cathode rostral (n = 6)
-Behavioural:
1. Hindlimb use: no difference between ES groups, both better than control
2. Inclined plane: Cathode rostral group better than anode rostral (p < 0.05), which were better than SCI only (p < 0.05)
-Histological: Cathode rostral group had more neurofilament stained axons than other groups
Dimitrijevic, Gerasimenko and Pinter (1998) -Model: Humans
-Injury: complete (AIS A), chronic (>1yr) SCI
-Quadripolar epidural stimulation at vertebral level T11-L1 -Frequency: 25-60 Hz, 0.2-0.5ms
-Intensity: 5-9V
n = 6, all participants received stimulation -Rhythmic, alternating stance and swing phases of the lower extremities were elicited with stimulation at the L2 segment
Borgens, Toombs et al (1999) -Model: dogs (various species)
-Injury: complete thoracic SCI dogs after intervertebral disk herniation or trauma
-Implanted OFS (epidural) across the SCI for 6 months -Intensity: 600μA from constant current stimulator alternating polarity every 15min
-Power supply: DC, 3.6V Li battery
-Electrodes: Pt:Ir on either side of the SCI
-ES: 600uA (n = 20)
-Sham OFS (n = 14)
-Behavioural (6-month follow-up):
1. Superficial pain: more recovery in OFS group (p = 0.0002)
2. Deep pain: no difference between groups (p = 0.11)
3. Proprioception and ambulation: no difference between groups (p = 0.43 and 0.22, respectively)
4. Combined score: more improvement in OFS group (p = 0.047)
-Neurophysiological: No difference between groups (p = 0.13)
-Adverse Effects: no
Moriarty, Borgens et al. (2001) -Model: Sprague-Dawley female rats
-Injury: T10 dorsal penetrating SCI
-Implanted oscillating field stimulation (OFS) (epidural) across the SCI for 4 weeks -Intensity: 40μA alternating polarity every 15min
-Power supply: DC, 3V Li Cell
-Electrodes: 90:10 Pt:Ir on either side of the SCI
-ES: OFS (n = 7; 4 replaced due to stimulator malfunction)
-Sham OFS
-Histological: OFS decreased astrocytes in SCI region
Gerasimenko, Makarovskii and Nikitin (2002) -Model: Humans
-Injury: complete (AIS A), chronic (>1yr) SCI
-Bipolar epidural stimulation from T10-L2 -Frequency: 1-120 Hz
-Intensity: 1–20 V
n = 8, all participants received stim -In most cases, L2 stimulation evoked unilateral stepping. Bilateral stepping in three subjects.
Herman, He et al. (2002) -Model: Human
-Injury: C5/6 (AIS C), 3.5 years post-SCI
A pair of Pisces-Quadplus electrodes were implanted over the upper lumbar enlargement -Long pulse durations (eg, 0.8 msec) were essential
-Frequency: 20-60 Hz, found to be comparatively less sensitive
-Intensity: above sensory threshold (sense of `parasthesia or vibration') but below that causing motor contraction
n = 1
-the participant received partial weight bearing training prior to electrode implantation and again afterwards in combination with stimulation
-Combination of training and stimulation resulted in a well-organized, smoother stepping pattern at higher treadmill rates and self-supported body weight, considerable improvement in endurance and speed during over-ground walking and reduced sense of effort
-After four months of over-ground training with stimulation, the subject could ambulate 270 m
Gerasimenko, Nikitin and Lavrov (2003) -Model: cats
-Injury: decerebration followed by spinalization at T10-12
-Unipolar epidural stimulation from L1-S1 -Electrodes: spring electrode with disc
-Frequency: 1-100 Hz
-Intensity: 10-200 uA, pulse duration 0.1msec
n = 8, all animals received stim -Locomotor activity occurred with stimulation between L4 and L5
Fujiki, Kobayashi et al. (2004) -Model: Sprague-Dawley female rats
-Injury: T7 hemisection
Intermittent bipolar ES (epidural) across the SCI, 24h prior to lesioning and repeated every 24h for 7 days -Voltage applied: double voltage threshold for motor evoked potential
-Frequency: 500Hz, 10 pulses/train every 10 seconds for 2h (720 trains)
-ES with no SCI (n = 3)
-ES with SCI surviving 6h (n = 3)
-ES with SCI surviving 24h (n = 3)
-ES with SCI surviving 1 week (n = 6)
-ES with SCI surviving 3 weeks (n = 3)
-ES with SCI surviving 8 weeks (n = 6)
-Histological: ES groups had increased GFAP staining (diffusely and focally at electrode site)
1. 24h post-SCI: ES with SCI group had less necrosis, hemorrhage and neutrophilic infiltration with smaller lesion /cavity
2. 1st and 3rd week post-SCI: ES with SCI group had smaller lesion/cavity, increased GFAP, vimentin, and GAP-43 staining
3. 8th week: no difference in lesion size/cavity between groups
Brus-Ramer, Carmel et al. (2007) -Model: Sprague-Dawley female rats
-Injury: unilateral pyramidotomy (PTx) transection contralateral to ES
-Intermittent constant current bipolar ES (epidural) on intact pyramid (contralateral to the lesion) for 6h daily for 10 days beginning post-operative day 1 -Intensity: minimum required for forelimb contraction (35-120μA)
-Power supply: constant current stimulator
-Frequency: 333Hz for 45ms every 2seconds
-Electrodes: stainless steel implanted at the time of PTx
-Sham ES with no PTx (n = 9)
-PTx only (n = 8)
-ES only (n = 7)
-ES and PTx (n = 8)
-Neurophysiological: lower activation threshold for ES+PTx group (strong ipsilateral motor activation; the sum of effects of PTx alone and ES alone were equal to the ES+PTx group
-Histological: ES with PTx group had greatest increase in CST axon terminations (equal to sum effects of PTx alone and ES alone), axon length, and axon terminal varicosity density in ipsilateral grey matter; ES and PTx group had greatest topographical outgrowth in the ventral grey matter, contralateral CST axons re-crossing midline, and contralateral grey matter CST axon density
Hentall, Burns (2009) -Model: Sprague-Dawley (ES experiment) and Fisher (neurophysiology experiment) female rats
-Injury: thoracic contusion (neurophysiology experiment) via impactor (4mm tip causing 3kdyn force for 20ms displacing cord 0.95mm)
and T8 contusion (ES experiment) via 10g weight (2mm diameter) drop from 12.5mm
-Implanted intermittent DC ES (to NRM) every 5 minutes for 12 h every day beginning 30min-1 h after SCI (stimulator implanted within 60min of SCI or 5-7 days prior) -Intensity: 30uA
-Power supply: 3V (2 x1.5V in series) silver oxide battery
-Frequency: 8Hz every 5 minutes for 12h every day for approximately 3d (mean battery life 3.2d)
-Electrodes: Tungsten cathode and stainless steel anode
-SCI only (n = 6)
-ES and no SCI (n = 4)
-No ES or SCI (normal) (n = 6)
-Sham ES with SCI (n = 13)
-ES with SCI (n = 14)
-Behavioural:
1. BBB score: no difference between groups from having implants
2. Tail-flick test: Prolonged latencies 7-15 days after implant in ES group
3. Von Frey allodynia test: ES with SCI group had less forepaw (hindpaw, no difference) and allodynia than sham ES with SCI, which had more allodynia than normal group in forepaw and hindpaw
-Neurophysiological: Normal group had more neutral cells than SCI only group and less spontaneous firing from on-cells and off-cells than ES with SCI group; sham ES with SCI rats had weaker on- and off-cell responses to noxious stimuli above lesion than normal rats
-Histological: More myelination in ES with SCI, but no difference in lesion size/cavity or NeuN staining, though less GFAP
Li, Brus-Ramer et al. (2010) -Model: Sprague-Dawley female rats
-Injury: unilateral PTx transection contralateral to ES
-Intermittent constant-current bipolar ES (epidural) on intact pyramid for 6h every day for 10 days beginning post-operative day 1 -Intensity: minimum required for forelimb contraction (35-120uA)
-Power supply: constant current stimulator
-Frequency: 333Hz for 45ms every 2seconds
-Electrodes: stainless steel implanted at time of PTx
- ES and PTx (n = 4)
-Sham ES and PTx (n = 4)
-Histological: ES with PTx group had more BrdU+ cells (proliferating) in dCST, BrdU+ cells apposing axons, OPCs, mature proliferating OLs, and OPCs differentiating into OLs; No difference in proliferating astrocytes or endothelial cells between groups
Carmel, Berrol et al. (2010) -Model: Sprague-Dawley female rats
-Injury: unilateral PTx contralateral to cortical ES
-Intermittent constant-current bipolar ES (epidural) on intact CST motor cortex (contralateral to the lesion) for 6h every day for 10 days beginning post-operative day 1 -Intensity: minimum required for forelimb contraction (1.1-1.8mA)
-Power supply: constant current stimulator
-Frequency: 333Hz for 45ms every 2seconds
-Electrodes: stainless steel implanted >1 week prior to PTx
-ES and PTx (n = 5)
-Sham ES with PTx (n = 5)
-Behavioural:
1. Horizontal ladder test: ES and PTx group had improvement of affected forelimb over time and returned to baseline scores; Sham ES had no improvement of forelimb with worsening from baseline; difference between groups at days 20 and 30; ES with PTx group had reduction in all error types beginning at day.
-Histological: ES with PTx group had increased axon density in ipsilateral grey matter, overall length of axons with a similar topographic distribution, had dorsal horn outgrowth (muscle and cutaneous receptor terminations), motor laminae outgrowth but not superficial dorsal laminae (nociceptive afferent terminations)
Carmel, Kimura et al. (2013) -Model: Sprague-Dawley female rats
-Injury: unilateral PTx contralateral to ES
-Intermittent constant-current bipolar ES (epidural) on intact CST motor cortex (contralateral to the lesion) for 6h every day for 10 days beginning post-operative day 1 -Intensity: minimum required for forelimb contraction (1.1-1.8mA)
-Power supply: constant current stimulator
-Frequency: 333Hz, 45ms, for 0.2ms duration every 2 seconds
-Electrodes: stainless steel implanted >1 week prior to PTx
-ES with PTx
-PTx alone
-Total: n = 17
-Histological: no difference in cortical cellular architecture or GFAP staining between groups due to implants
1. Spinal Cord: ES with PTx group had greater total axon length in ipsilateral grey matter
2. Cuneate nuclei: ES with PTx group had greater total axon length in ipsilateral and contralateral grey matter;
3. Parvocellular nuclei: ES with PTx group had greater total axon length in ipsilateral and contralateral grey matter;
4. Magnocellular nuclei: ES with PTx group had greater total axon length in ipsilateral and contralateral grey matter; ES increases growth bilaterally with similar topographical distribution (thus greatest outgrowth in red nucleus that restore function)
-Number of axons re-crossing midline in SC greater in ES with PTx.
Carballosa-Gonzalez, Vitores et al. (2014) -Model: Sprague-Dawley female rats
-Injury: T8 contusion via 10g weight (2mm diameter) drop from 12.5mm
-Single session ES (to nucleus raphe magnus (NRM)) every 5minutes for 2h starting 72h after SCI -Intensity: 30uA
-Frequency: 8Hz every 5 minutes for 2h with a pulse width of 1ms
-Electrodes: Tungsten
-Sham ES and SCI (n = 4)
-No ES or SCI (normal) (n = 4)
-ES with SCI (n = 4)
CREB/PKA and pCREB/pPKA experiment
-No ES or SCI (normal) (n = 7)
-No ES with SCI (n = 8)
-ES with SCI (n = 7)
-Histological: ES with SCI group had higher cAMP levels in cervical, thoracic and lumbar tissue with return to near-normal levels; pimozide use reduced cAMP levels those in SCI (ES failed to increase it afterward)
-PKA and CREB higher in SCI animals with ES reversing this increase
-pPKA/PKA and pCREB/CREB reduced after SCI and increased with ES
Carmel, Kimura et al. (2014) -Model: Sprague-Dawley female rats
-Injury: unilateral PTx contralateral to ES
Intermittent constant-current bipolar ES (epidural) on intact CST motor cortex (contralateral to the lesion) for 6h every day for 10 days beginning 8 weeks after PTx -Intensity: motor threshold (minimum required for forelimb contraction; 0.9-1.7mA)
-Frequency: 333Hz, 0.2ms biphasic pulse, 45ms duration, every 2 seconds
-Electrodes: stainless steel implanted 5 weeks after PTx
-Power supply: constant current stimulator
-ES with PTx (n = 5)
-Sham ES+PTx (n = 5)
-Behavioural:
1. Horizontal ladder test: ES with PTx group had more improvement with errors back to baseline at week 11; muscimol use in ES with PTx resulted in transient re-emergence of errors with no change in subtypes of errors (ES after chronic PTx improves recovery through intact M1 to impaired forelimb connections)
Fujiki, Kobayashi et al. (2004) -Model: Sprague-Dawley female rats
-Injury: unilateral hemisection
-ES (at T7 level of spinal cord) 24 hrs before injury, immediately following SCI and then every 24hrs for 7 days -Intensity: 2x threshold voltage of spinal cord evoked potential
-Frequency: 500 Hz, 10
pulses/train, at an inter-train interval of 10 sec
-Duration: 2 h
-Electrode: bipolar flexible wire
-Preconditioning stimulation, no SCI (n = 3)
-SCI only with survival time: 6hr (n = 3), 24hr (n = 3), 1 week (n = 6), 3 weeks (n = 3), 8 weeks (n = 6)
-ES and SCI with survival time: 6hr (n = 3), 24hr (n = 3), 1 week (n = 6), 3 weeks (n = 3), 8 weeks (n = 6)
-Histological: Upregulation of glial fibrillary acidic protein (GFAP) and vimentin immunoreactivity were increased at 1 week after injury in the rats treated with electrical stimulation
-Preconditioning electrical stimulation of the spinal cord activated reactive astrocytes, then significantly attenuated edema, progressive necrosis, and cavitation, especially in the secondary cavity lesions
Ichiyama, Gerasimenko et al. (2005) -Model: Sprague-Dawley female rats
-Injury: transection (T7-T9)
-Continuous epidural stimulation at 2, 3 or 4 sites between T12 and L6, 2-3 weeks post-SCI - Frequency: 30, 40 or 50 Hz, 200 us duration rectangular pulses
- Intensity: 0-13 V
n = 6, all animals received stim -Bilateral hindlimb locomotor activity was evoked most often with epidural stimulation at 40–50 Hz applied at L2. Providing >5% body weight support was necessary for locomotion
Shapiro, Borgens, et al. (2005) -Model: Humans
-Injury: complete motor and sensory SCI between C5 and T10, no transection demonstrated on MRI
-Oscillating field stimulator (OFS) implanted within 18 days of SCI and explanted at 15 weeks
-Three electrodes were placed above and below level of injury
-Unit had an onboard oscillator timed
for 15-minute intervals and delivered a field of 500 to 600 mV/mm and a current density of 42.4 mAmp/mm2 to each electrode
-10 participants received OFS. -One participant lost to follow up after 6 months -No complications at insertion of OFS
-Significant improvement in pinprick sensation and motor status at 1 year post-SCI, as compared to baseline
Lavrov, Gerasimenko et al. (2006) -Model: Sprague-Dawley female rats
-Injury: transection T8
-Epidural stimulation at S1 spinal cord level During Reflex Testing:
- single stimuli, duration 0.5ms
- Frequency: 0.2, 1, 3 and 5 Hz
-Intensity: between 0.5 and 10 V
During locomotion:
- Continuous stimulation
-Frequency: 40 Hz (25 ms pulse interval) and a pulse duration of 0.2 ms
Total n = 9, recorded from 4 rats pre-transection and 7 rats following transection
Epidurally-induced (S1) spinal cord reflexes:
-The late response was abolished following transection and reappeared after 3 weeks and increased, whereas the middle response was facilitated and progressively increased following transection
-Behavioural: restoration of stepping coincided with reappearance of the late response
Ichiyama, Courtine et al. (2008) -Model: Sprague-Dawley female rats
-Injury: transection T9
-Continuous epidural stimulation at L2 throughout step trainings (7d/week, 30 min/session for 6 weeks)
-Frequency: 40 Hz with 200 us duration rectangular pulses
-Non-injured (n = 10)
- SCI and step trained (n = 5)
- SCI and no step training (n = 5)
-Histological: significantly lower number of FOS+
neurons in trained versus nontrained rats throughout lumbosacral segments after 1 hr of stepping
-Behavioural: trained rats had higher and longer steps, narrower base of support at stance, and lower variability in EMG parameters
Lavrov, Courtine et al. (2008) -Model: Sprague-Dawley female rats
-Injury: transection (T8) and unilateral deafferentation (T12-S1)
-Epidural stimulation at S1 spinal cord level During Reflex Testing:
-single stimuli, duration 0.5ms
-Frequency: 0.2, 1, 3 and5 Hz
-Intensity: between 0.5 and 10 V
During locomotion:
-Continuous stim
-Frequency: 40 Hz (25 ms pulse interval) and a pulse duration of 0.2 ms
-Control (n = 5)
-Transection and deafferentation (n = 4)
-All animals were able to generate stepping-like patterns on a moving treadmill on the non-deafferented, but not deafferented, side from 3 to 7 weeks after surgery when facilitated by epidural stimulation
-Spinal-cord-evoked potentials were observed on both sides, although middle (monosynaptic) and late (long latency) responses were more prominent on the non-deafferented side.
Courtine, Gerasimenko et al. (2009) -Model: Sprague-Dawley female rats
-Injury: transection (T7)
-L2 and/or S1 epidural stimulation
-Frequency: 40–50 Hz
-Intensity: 1–4 V
rectangular pulses (0.2 ms duration)
n = 8, trained for 8 weeks beginning 8 days post-transection
n = 6, trained for 3 weeks
n = 7, untrained
-Combinations of serotonergic agonists and epidural electrical stimulation were able to acutely transform spinal networks from nonfunctional to highly functional and adaptive states as early as 1 week after transection
-Behavioural: full weight bearing treadmill locomotion following SCI was observed
Harkema, Gerasimenko et al. (2011) -Model: Human
-Injury: C7/T1 absent voluntary motor function and partial preservation of sensation below T1 (AIS B)
-Tonic epidural stimulation of L1-S1 spinal cord segments with a 16-electrode array Within a session, stimulation duration
ranged from 40 to 120 min
-Intensity: 0.5 to 10.0 V -Frequency: 5 to 40 Hz with either a 210 μs or 450 μs pulse width
n = 1
-The participant received 170 locomotor training sessions (body-weight supported treadmill training) over 26 months prior to electrode implantation
-Epidural stimulation enabled full weight-bearing standing with assistance provided only for balance for 4.25 min
-7 months after implantation, the patient recovered supraspinal control of some leg movements, but only during epidural stimulation.
Wenger, Mourad et al. (2014) -Model: Lewis female rats
-Injury: transection (T7)
-Closed-loop neuromodulation system including epidural stimulation at L2 and S1 spinal cord level -Frequency, amplitude, and pulse width of EES were adjusted to cover the entire range of values that promoted functional movements
-Frequency: 20 to 90Hz
-Characterization of relationships between EES frequency and gait pattern modulation (n = 5)
-Real-time control tested daily over a period of 4 weeks, starting 5 weeks post-lesion (n = 3)
-Optimized a neuromodulation in real time to achieve high-fidelity control of leg kinematics during locomotion in rats
-established a technological platform with embedded control policies that integrated robust movement feedback and feed-forward control loops in real time
-Animals with complete spinal cord injury performed more than 1000 successive steps without failure, and were able to climb staircases with precision
Rejc, Angeli and Harkema (2015) -Model: Human
-Injury: motor complete (AIS A or B) above T10, chronic (>1yr) SCI
-A 16-electrode array with a wide-field electrode configuration with cathodes positioned caudally was implanted over the spinal cord segments L1-S1 -Intensity: near-motor threshold stimulation amplitude that did not directly elicit lower limb movements
-Frequency: 25 Hz
n = 4
After implantation all participants underwent 80 sessions of stand training with stimulation (1 hour, 5 sessions per week)
-Standing with the least amount of assistance was achieved with individual-specific stimulation parameters, which promoted overall continuous EMG patterns in the lower limb 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.
-Negligible EMG activity of lower limb muscles by epidural stimulation during sitting
Capogrosso, Milekovic et al. (2016)
-Model: male rhesus monkeys (Macaca mulatta)
-Injury: approximately two-thirds of the dorsoventral extent of the spinal cord at T7
-Implanted intracortical electrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant (at T13–L1 vertebrae) and a pulse generator Mapping leg muscles:
-Single pulses of cathodic monopolar, charge-balanced stimulation (0.3 ms, 1 Hz)
During locomotion:
-Frequency: 30–80 Hz
-Intensity: 1.5–3.9 V
Total n = 9
Of those, n = 2 received SCI
-Development and validation of selective spinal cord simulation protocols was possible
-Behavioural: stimulation restored weight-bearing locomotion of the paralyzed leg on a treadmill and over ground
Rejc, Angeli et al. (2017) -Model: Human
-Injury: chronic motor complete SCI (AIS A or B) above T10, chronic (>1yr) SCI
-A 16-electrode array was implanted over the spinal cord segments L1-S1 -Intensity: 0.1V to 5 V
-Frequency: 21-31 Hz to induce a rhythmic EMG pattern
n = 4
After implantation all participants underwent 80 sessions of stand training with stimulation (1 hour, 5 sessions per week) followed by 80 sessions of step training with stimulation (1 hour, 5 sessions per week)
-Step training performed after a bout of stand training substantially impaired standing ability in three of the four individuals
-Poorer standing ability was associated with more variable EMG patterns that alternated EMG bursts and longer periods of negligible activity in most of the muscles
-Stand and step training with epidural stimulation were not sufficient to improve motor function for standing without stimulation
Rejc, Angeli et al. (2017) -Model: Human
-Injury: motor complete (AIS B) C7 SCI
-A 16-electrode array was implanted over the spinal cord segments L1-S1 -Stimulation parameters are variable, depending on the training (standing, stepping or voluntary movement) n = 1
Data collected over 4.1 years, individual participated in a number of activity-based interventions in combination with epidural stimulation
-Progressive recovery of voluntary leg movement and standing without epidural stimulation in an individual with chronic, motor complete SCI over a number of years of activity-based interventions utilizing stimulation configurations customized for the different motor tasks that were specifically trained (standing, stepping, volitional leg movement)
Lo, Kuan et al. (2017) -Model: Sprague-Dawley female rats
-Injury: transection (T8)
-Custom epidural 18-electrode array over lumbosacral segments Non-transected, awake rat:
monophasic stimulus
-Frequency: 0.5 Hz
-Intensity: 0.3 mA
Rats with transection:
bi-phasic stimulus
- Frequency: 40 Hz, 0.2
ms pulse width
-Intensity: 0.7 mA
-Neurologically intact rat (n = 1)
-Spinal cord transection (n = 1)
Wireless, fully integrated system-on-a-chip was shown to record EMG while providing epidural stimulation to facilitate standing and stepping following spinal cord transection
Jack, Hurd et al (2017) -Model: Lewis female rats
-Injury: C4 dorsal lateral quadrant
Single session ES (to forelimb motor cortex) for 30min immediately before SCI -Electrodes: two tungsten electrodes (5 μm diameter, 0.1 MΩ impedance) inserted to depth of 1.5mm. Frequency 20 and 333Hz
-Power supply: constant current stimulator
-Sham (n = 10)
-SCI only (n = 10)
-SCI +20Hz (n = 14)
-SCI +333Hz (n = 14)
Behavioral: Montoya staircase test showed no difference between stimulated or SCI only groups
Histological: No difference in axonal regeneration was between groups. Increased axonal collateralization was found in ES333 animals compared with controls
Zareen et al. (2018) -Model: Sprague-Dawley female rats
-Injury: bilateral moderate C4 contusion
Bilateral intermittent theta burst (iTBS) ES (epidural) of motor cortex for 30 minutes every day for 10 days beginning 7 weeks after SCI combined with concurrent continuous cathodal transspinal direct current stimulation -Intensity iTBS: 75% motor threshold
-Intensity of spinal cord stimulation: 1.5 mA
-SCI only (n = 10)
-ES+SCI (n = 9)
Histological: no between-group lesion size difference; enhanced CST outgrowth below and above the lesion in stimulation group.
Behavioral: 23% significant improvement in horizontal ladder task with stimulation compared with non-significant 7% improvement injury nly; Significant improvement in IBB task scores in stimulation group (5.77 to 6.79) and non-significant change in SCI only group (5.05 to 5.42).
Batty, Torres-Espín et al. (2020) -Model: Lewis female rats
-Injury: C4 dorso-lateral quadrant lesion
-Single session ES (to forelimb motor cortex) for 30min immediately following SCI -Intensity: 1.1x motor threshold (0.6-1.3mA)
-Frequency: 333Hz, 0.2ms biphasic pulse, every 0.5 seconds
-Electrodes: two tungsten electrodes (5 μm diameter, 0.1 MΩ impedance) inserted to depth of 1.5mm
-Power supply: constant current stimulator
SCI and ES and upper extremity rehabilitative training (n = 11)
-SCI and no ES and rehabilitative training (n = 9)
-Behavioural:
Single pellet reaching: ES group showed increased functional recovery compared to no ES group
-Histological:
1. Significant increase in sprouting of corticospinal tract collaterals above the lesion site in ES versus control
2. No difference in regeneration through lesion site between groups