Table 2.

Transcutaneous electrical spinal stimulation studies demonstrate stimulation at multiple spinal sites using a variety of stimulation parameters can ameliorate spinal sympathetic dysfunction(s)

Study	Protocol	Electrode Placement, Number, and Size; Stimulation Parameters and Stimulator	Autonomic Outcome(s)
1. Sachdeva et al. (23)	Protocol A (TSCS to prevent AD): 1) Digital anorectal stimulation (DARS) without TSCS 2) TSCS then DARS Protocol B (TSCS to interrupt AD): 1) DARS to trigger AD then 2) TSCS initiated 30 s after DARS	C: T7–T8 (V, P) 1 × 3 cm round A: L + R iliac crests 2: 5 × 9 cm Freq: 30 Hz Width: 2 ms Shape: rectangular (rect), biphasic Amp: 20–30 mA Digitimer DS5	TSCS both prevented and reduced DARS-induced increase in SBP Protocol A Prevention: 1) without TSCS, DARS ↑ SBP by 29 ± 5 mmHg: AD is ↑ SBP > 20 mmHg 2) with TSCS, DARS ↑ SBP by 5 ± 3 mmHg Thus DARS-induced ΔSBP was 82% less when preceded by TSCS* Protocol B Treatment: 1) without TSCS, DARS ↑ SBP by 18 ± 1 mmHg 2) after TSCS, SBP ↓ by 9 ± 4 mmHg Thus, TSCS reduced DARS-induced rise in SBP by ∼50%, when applied after DARS *TSCS also reduced DARS-induced reflex pelvic floor EMG activity
2. Wu et al. (24)	TSCS was delivered intermittently while seated, at rest, for the duration of the motor study (duration not stated). Study examined the effects of single and paired pulses of TSCS on the latency and amplitude of motor responses in muscles of the arm and hand.	C: T2–T4 V, P 5 x 10 cm placed longitudinally A: C4–C5 V, A 5 × 10 cm placed horizontally ∼2–3 cm superior to sternal notch Grounds: L + R clavicles, 2: 5 × 10 cm Freq: 0.2 Hz Width: 2 ms Shape: rect, biphasic Amp: 4.4–102 mA, 100—175% of resting motor threshold (RMT) of the abductor pollicis brevis (APB) Digitimer DS7A or DS8R	Safety and Tolerability Data Changes to resting BP ↑ MAP > 20% over baseline for at least 15 min (n = 7/13 with SCI and in 0/14 able-bodied (AB) controls)* ↓ MAP by 20% or more from baseline for at least 15 min (n = 2/13 SCI and 0/14 AB) Changes to resting HR ↑ HR by 20% or more from baseline for at least 15 min (n = 1/13 SCI and 0/14 AB) ↓ HR by 20% or more from baseline for at least 15 min (n = 7/13 SCI and 1/14 AB) *Authors reported these increases to be like those seen during peripheral nerve stimulation alone. These increases appeared solely or predominantly in those with cervical SCI and not in either AB controls or participants with ALS (n = 4).
3. Sayenko et al. (25)	All participants received TSCS, no stimulation, and “sham” TSCS during assisted standing in a custom frame to assess ability to stand. 1 testing day (2 h, n = 15/15), and/or 12 training sessions (2 hours, n = 6/15)	C: T11–T12 or L1–L2 V, P, 3.2 cm round A: L + R iliac crests 2: 7.5 × 13 cm Freq: 15 Hz* Width: 1 ms, filled with 10 kHz carrier wave Shape: rect, monophasic Amp: <150 mA Custom built constant current stimulator *selected as most effective for standing, [tested 0.2–30 Hz]	Safety, Tolerability, and Anecdotal Data ↑ sweating below lesion during first session (n = 3/15) Authors reported that if symptoms of OH occurred, they were readily mitigated by adjusting stimulation intensities No bouts of AD were observed ↑ SBP by more than 60 mm Hg during first session at a very low stimulation intensity (10 mA), with no further incidents following first session (n = 1/15)
4. Gad et al. (26)	4-wk (2×/wk) hand grip strength program with TSCS. TSCS delivered during 18 MVC attempts in middle of each 1–2 h training session	C: 1) C3–C4 and 2) C6–C7 V, P 2: 2 cm round A: L + R iliac crests 2: 5 × 10 cm Freq: 30 Hz filled with 10 kHz carrier wave Width: 1 ms Shape: rect, biphasic (for AIS C) or monophasic (for AIS B) Amp: 10–250 mA NeuroRecovery Technologies multi-channel stimulator	Anecdotal Data ↑ sweating ability generally or below level of lesion (n = 2/6)
5. Phillips et al. (20)	Protocol to elicit orthostatic hypotension (OH) and then assess if TSCS can treat OH-related symptoms: 1) 25 min rest, supine, then; 2) Induce orthostatic challenge (OC: tilt table) and when systolic BP ↓ by 20 mmHg then; 3) TSCS	C: T7/T8 V, P 3 cm round A: L + R iliac crests 2 × 5 × 9 cm Freq: 30 Hz Width: 1 ms Shape: rect, monophasic Amp: 10–70 mA until BP normalized (>1 min) Stimulator NR	TSCS normalized OH-induced decreases in BP and cerebral blood flow TCSC increased SBP, DBP, MAP, and middle and posterior cerebral artery blood flow to baseline levels (after OC reduced these measures) OH symptoms (e.g., dizziness) were reduced with TSCS HR became elevated, CO and SV were reduced with OH and were not changed with TSCS during OC *Authors noted that leg muscle EMGs were recorded to confirm no activation and therefore no TSCS-induced pressor-related effects on BP
6. Gad et al. (27)	1) Participant walked using EKSO alone for 4 wk, then; 2) 1 wk of EKSO + TSCS, then; 3) 1 wk of EKSO + monoamine agonist buspirone (10 mg, 2/day), then; 4) 1 wk of EKSO + TSCS + buspirone. Training = 1 h/day, 5 days/wk.	C: T11/T12 and/or Co1 V, P, 2.5 cm round A: L + R iliac crests 2: 5 × 10.2 cm Freq: 30 Hz over T1/12 5 Hz over Co1 Width: NR* Shape: NR* Amp: determined by efficacy and comfort* Stimulator NR*	Anecdotal HR, BP, and self-reported sweating outcomes HR during stepping with EKSO alone increased minimally with EKSO + TSCS (by ∼10 beats/min, from ∼70 to ∼80 beats/min) and by ∼10 beats/min with EKSO + buspirone (to ∼90 beats/min) but ↑ substantively during stepping with TSCS + buspirone (to ∼135 beats/min) BP during stepping generally similar throughout protocol (∼ 140/95 mmHg EKSO alone; ∼ 150/90 EKSO + TSCS; 152/92 EKSO + TSCS + buspirone) ↑ self-reported sweating score increased from 1/5 (EKSO alone) to 3/5 (TSCS alone) to 5/5 (TSCS + buspirone) *based on reference to 38, assume stimulation is with 10 kHz carrier wave; Width: 0.3—1 ms; Shape: rect, biphasic; Amp: 30—200 mA
7. Murray and Knikou (28)	1) Baseline TMS-elicited motor evoked potentials recorded in extensor and flexor carpi radialis muscles; single and dual pulse (inter-pulse interval ranged: 1–30 ms) stimulus paradigms, then; 2) Participant received ∼55 min of TSCS while supine for 14 sessions (over a 3 wk period); to avoid exhaustion and facilitate spontaneous neuron depolarization, stim delivered in 10 min blocks, then; 3) TMS protocol repeated after treatment period	C: C5–T2 V, P 10.2 × 5.1 cm, placed vertically A: L + R clavicles 10.2 × 5.1 cm Freq: 0.2 Hz Width: 1 ms Shape: rect, monophasic Amp: intensities ranged from 5–68, mean 42 mA. Intent was to use intensities ranging from below motor threshold to intensities that evoked bilateral muscle contractions Digitimer DS7A triggered by CED Spike 2 scripts	Anecdotal self-reported sweating outcome During the intervention (Protocol step 2) participant reported he had started to sweat in the upper back and armpits, a response that had stopped after the injury
Shelyakin et al. (29)	1) Electrode placement was individualized, NR 2) Treatment consisted of 20 sessions (20–50 min each) of direct current stimulation 3) Motor outcomes were different for each of the 25 patients with chronic SCI or tuberculous spondylitis	C and A: Placed along the vertebral column, “positions and distance between electrodes were changed depending on the clinical effect obtained and the nature of changes in electrophysiological measures” Agar electrodes, 600 mm2 Direct current stim Amp: <10 mA	Anecdotal HR Outcomes ↑ HR from 95–100 (baseline) to up to 120 beats/min during direct current stimulation treatment sessions, authors proposed this effect “is probably due to the direct action of the direct current on ganglia of the sympathetic nervous system located along the spinal cord.”

A, anode; ant, anterior; AD, autonomic dysreflexia; C, cathode; CO, cardiac output; EMG, electromyogram; EKSO, exoskeleton; HR, heart rate; MAP, mean arterial pressure; NR, not reported; OC, orthostatic challenge; OH, orthostatic hypotension; P, posterior; PT, physical therapy; S, spinal; SBP, systolic blood pressure; SV, stroke volume; TMS, transcranial magnetic stimulation; TSCS, transcutaneous spinal cord stimulation; V, vertebral.