A scoping review of novel spinal cord stimulation modes for complex regional pain syndrome

Figures & data

Table 1. Characteristics of studies included in the systematic review: Participants, interventions, and comparators.

Study, number of patients, type of study	Participants and pain syndromes	Intervention: Details of paresthesia-free SCS	Comparator group	SCS lead type and position	Therapies tried prior to paresthesia-free SCS
Case reports/series
Al-Kaisy et al.^Citation12 2015 (n = 15) CS (R)	Age: 46 ± 12 years M/F: 5/6 Pre-intervention: NRS pain: 8.2 ± 1.7 BPI 57.6 ± 9.4 painDETECT 29 ± 8 PCS 33 ± 11 CRPS (6 patients): UL (3), LL (3) (IASP Budapest criteria used) Duration of CRPS: NP	Type: HF-10 F: 10 kHz PW: NP A: 0.5−3.5 mA Intraoperative testing with PB-SCS to ensure >80% overlap of stimulation with patients’ pain locations	—	Trial type: Percutaneous or tunneled SCS leads: 1–2 octopolar cylindrical leads Lead level: UL: C2–C7 LL: T8–T12	CMM: TCA, gabapentinoids, opioids Topical treatments Physical therapy TENS CBT
Crapanzano et al.^Citation17 2017 (n = 1) CR (R)	Age: 53 years F CRPS knee and thigh (spread to bilateral arms/shoulders over time) NRS pain: NP Duration of CRPS: 7 years	Type: HF-10 F: 10 kHz PW: NP A: NP	—	NP	CMM: Opioids, NSAIDs, TCA, SNRI, gabapentinoids Topical treatments Physical therapy LSB
Kriek et al.^Citation18 2015 (n = 1) CR (R)	Age: 65 years F CRPS: UL NRS pain: 8 Duration: 16 years	Type: Burst F: 500/40 Hz PW: 1000 ms A: 0.225	Failure of PB-SCS after 4 years of good analgesia F: 60 Hz PW: 387 ms A: 5.8V	Trial type: NP SCS lead: 1 octopolar cylindrical lead Lead level: NP	CMM: NSAIDs, TCA, pregabalin sympathetic blockade TENS Physical therapy
Reddy et al.^Citation19 2016 (n = 2) CS (P)	Age: 56.5 years M/F: 0/2 CRPS lower extremity NRS pain: 8 (6–10)^a Duration: 1.6 (0.4–2.9) years	Type: HF-10 F: 400 Hz–10 kHz PW: NP A: 0.5–10 V	—	Trial type: NP SCS lead: NP Lead level: T8–T11	NP
Smith et al.^Citation20 2015 (n = 1) CR (R)	Age: 70 years F CRPS back and LL NRS pain: 6 Duration: 20 years (?)	Type: HF F: 1.15 kHz PW: 120 ms A: 5.0 V	Failure of PB-SCS after 6 months of good analgesia F: 40 Hz PW: 330 ms A: 3.5 V	Trial type: SCS in situ SCS lead: paddle Lead level: top at caudal aspect of T8	CMM Physical therapy Epidural injections RF lesioning
Tate^Citation21 2017 (n = 1) CR (R)	Age: 56 years F CRPS right LL + phantom limb pain NRS pain: NP Duration: 12 years	Type: HF-10 F: 10 kHz PW: NP A: NP	Failed trial of PB-SCS due to intolerable paresthesias	Trial type: NP SCS lead: 2 leads (NP) Lead level: T8–T11	CMM Injections (NP) Conventional SCS trial: failed LSB (RF) Nerve blocks
Wille et al.^Citation13 2017 (n = 3) CS (R)	Age: 49 years M/F: NP CRPS: details NP NRS pain: 7.9 Duration: NP	Type: HD F: 130–1000 Hz (mean 409 Hz) PW: 150–1000 ms A: 2.4 V (subperception)	Failure of PB-SCS over time and unwanted paresthesias F: 30–60 Hz PW: 284 ms A: 3.3 V	Trial type: NP SCS lead: NP Lead level: as close as possible to T9–T10 disc interspace
Abstracts
Amirdelfan et al.^Citation22 2017 (n = 6) CS (R)	Age: NP M/F: NP CRPS UL (1) CRPS LL (5 – all except 1 had bilateral CRPS) NRS pain: 7.8 (mean) Duration: NP	Type: HF-10 F: 10 kHz PW: 30 ms A: individualized	—	Trial type: NP SCS leads: 1–2 octopolar cylindrical leads Lead level: UL: C2–C6 LL: T8–T11	NP
Santarelli et al.^Citation23 2016 (n = 7) CS (P)	Age: 39–75 years M/F: 5/2 CRPS: UL (2) LL (5) (IASP Budapest criteria used) NRS pain: 6–10 Duration: 9 months–4 years	Type: HF-10 F: 10 kHz PW: NP A: NP	—	Trial type: NP SCS leads: 1–2 octopolar cylindrical leads Lead level: UL: C2–C6 LL: T8–T11	NP
Smet and Van Buyten^Citation24 2016 (n = 1) CR (R)	Age: 59 years F CRPS: UL NRS pain: 7–10 Duration: > 1 year	Type: HF-10 F: 10 kHz PW: NP A: NP	Initial positive trial of PB-SCS but loss of effect	Trial type: NP SCS leads: 2 octopolar leads Lead level: C2–C5	CMM
Gulve et al.^Citation25 2015 (n = 1) CR (R)	Age: 63 years M CRPS: UL NRS pain: 7–10 Duration: 7 years	Type: HF-10 F: 10 kHz PW: NP A: NP	—	Trial type: percutaneous SCS lead: 1 octopolar lead Lead level: tip at C1/C2	CMM: opioids, TCA, gabapentinoid Physiotherapy
Wohak^Citation26 2013 (n = 3) CS (R)	Age: 37–48 years M/F: 2/1 CRPS: UL NRS pain: NP Duration: NP	Type: HF-10 F: 10 kHz PW: NP A: NP	PB-SCS with initial good result in one patient but failure after dislocation	Trial type: NP SCS lead: 1–2 octopolar leads Level: cervical spine	CMM: opioid, pregabalin, NSAIDs
Randomized controlled trial
Kriek et al.^Citation27 2017 (n = 29) RCT	Age: 42.6 ± 12.8 years M/F: 4/25 CRPS: UL (11), LL (18) VAS: 72.7 ± 2.6 mm Duration: 3 (1–5)	Type: Three groups: 500 Hz, 1200 Hz, Burst	Type: PB-SCS (40 Hz) and placebo groups	Trial type: NP SCS lead: 1 octopolar lead Level: NP but “optimal positioning with overlapping paresthesia in the painful area”	NP

SCS = spinal cord stimulation; CS (R/P) = case series (retrospective/prospective); M/F = male/female; NRS = numerical rating scale; BPI = Brief Pain Inventory; PCS = Pain Catastrophizing Scale; CRPS = complex regional pain syndrome; UL = upper limb; LL = lower limb; IASP = International Association for the Study of Pain; NP = not provided; HF-10 = high-frequency stimulation at 10 kHz; F = frequency; PW = pulse width; A = amplitude; PB-SCS = paresthesia-based spinal cord stimulation; CMM = conventional (non-SCS) medical management; TENS = transcutaneous electrical nerve stimulation; CBT = cognitive behavioral therapy; CR = case report; NSAIDs = nonsteroidal anti-inflammatory drugs; TCA = tricyclic antidepressants; SNRI = serotonin and norepinephrine reuptake inhibitors; LSB = lumbar sympathetic plexus block; HF = high-frequency stimulation; RF = radio frequency; HD = high-density stimulation; RCT = randomized controlled trial; VAS = visual analog scale.

Table 2. Characteristics of studies included in the systematic review: Outcomes including analgesic benefits and adverse effects.

Study, year, number of patients, type of study	Newer SCS mode	Follow-up time points after implantation	Outcomes assessed	Important results	Adverse effects of paresthesia-free SCS	Comments
Case reports/series
Al-Kaisy et al.^Citation12 2015 (n = 15) CS (R)	HF-10	1, 3, and 6 months	NRS pain BPI PCS EQ-5D painDETECT	At 6 months: NRS pain reduced by 59% BPI reduced by 45% PCS reduced by 75% EQ-5D increased by 101% Excellent or good satisfaction for 10/11 patients	No adverse effects related to paresthesia-free SCS	11/15 had successful trials but 3 of the 4 patients who had no benefit had CRPS of the foot; all 3 patients with CRPS of the hand responded
Kriek et al.^Citation18 2015(n = 1) CR (R)	Burst	24 months	NRS pain Medication intake Vasomotor and sudomotor symptoms ROM	NRS pain decreased by 75% Lower medication intake No worsening in vasomotor and sudomotor symptoms or ROM	—	Burst stimulation provides analgesia when tolerance develops to conventional SCS
Reddy et al.^Citation19 2016 (n = 2) CS (P)	HF-10	0.5 days	VAS pain Discomfort Feedback from patients	NRS pain reduced by 30%–50% Patients preference: HF		0.5-day trial of HF-SCS during weeklong conventional trial; possibility of carryover effects
Smith et al.^Citation20 2015 (n = 1) CR (R)	HF (1.15 kHz)	6 months	NRS pain QoL Medication intake Quality of sleep	NRS pain reduced by 50% Reduction of medication intake	—	Paresthesia-free (high-frequency) SCS mode used by patient to avoid intolerable paresthesias
Tate^Citation21 2017(n = 1) CR (R)	HF-10	4 months	NRS pain QoL Vasomotor and sudomotor symptoms Anxiety ROM Medication intake	100% pain relief with resolution of phantom limb pain, anxiety, and improved QoL Improvement in vasomotor and sudomotor symptoms ROM: improved gait Medication intake: opiate-free	—	—
Wille et al.^Citation13 2017(n = 3) CS (R)	HD	1, 6, and 12 months after switch from conventional to HD SCS	NRS pain	Significant and progressive decrease (7.9 to 3.1) in NRS pain scores following implementation of HD mode for 12 months in 2 patients on HD for this duration One patient with CRPS requested reprogramming to conventional SCS due to preference to PB-SCS (although effect of PF-SCS)	—	Possibility of a dose-related response between the amount of energy delivered to the spinal cord and clinical effect
Abstracts
Amirdelfan et al.^Citation22 2017 (n = 6) CS (R)	HF-10	4 to 15 months	VAS pain Medication usage Physical activity Vasomotor signs	Decrease in VAS pain scores by 83% ± 3.0% and medication usage Improvement in activity and vasomotor signs	—	All 6 patients responded
Santarelli et al.^Citation23 2016 (n = 7) CS (P)	HF-10	3, 6, 9, and 12 months	VAS pain scores Medication usage Quality of life (SF-36) CES-D scores PGIC Functional status (6-min walking test or hand grip test)	Follow-up ongoing at time of publication of abstract: long-term results not available for every patient At 3 months (n = 4): decrease in VAS pain scores (by 25%–100%) and in CES-D scores; improved ROM and PGIC scores At 12 months (n = 1): decrease in VAS pain scores to 0 at 12 months and decrease in CES-D scores by 66% with improvement in physical function	—	5 patients had positive trials and 1 patient had direct implant (due to diabetes)
Smet and Van Buyten^Citation24 2016 (n = 1) CR (R)	HF-10	12 months	NRS pain ROM wrist Medication intake	NRS pain reduced to 0/10 ROM in wrist improved Discontinuation of all analgesic medications	—	—
Gulve et al.^Citation25 2015 (n = 1) CR (R)	HF-10	18 months	NRS pain EQ-5D score Medications Functional improvement	NRS pain: 80% reduction EQ-5D score increased from 0.2 to 0.8 Discontinuation of all analgesic medications and able to resume pre-injury activities		No postural variation in analgesic effect and no sensory symptoms
Wohak^Citation26 2013 (n = 3) CS (R)	HF-10	4 to 8 months	NRS pain ROM Medication intake Vasomotor signs	NRS pain and hyperalgesia decreased by 80%–100% ROM: improvement	—
Randomized clinical trial
Kriek et al.^Citation27 2017 (n = 29) RCT	Three groups: 500 Hz, 1200 Hz, Burst	At the end of 2 weeks with each of the fove modes At the end of 3 months with the preferred stimulation mode	VAS for pain MPQ GPE Preference of type of stimulation	VAS pain: All PF-SCS settings were equi-analgesic and significantly better with higher GPE scores than placebo VAS pain scores were lower with preferred stimulation 52% of patients preferred nonstandard stimulation	No serious adverse effects	Various reasons for patients preferring particular modes: Amount of pain reduction Lack of paresthesia User-friendliness comfort Recharging time

SCS = spinal cord stimulation; CS (R/P) = case series (retrospective/prospective); HF-10 = high-frequency stimulation at 10 kHz; NRS = numerical rating scale; BPI = Brief Pain Inventory; PCS = Pain Catastrophizing Scale; EQ-5D = EuroQol–five dimensions; CR = case report; ROM = range of motion; HF = high-frequency stimulation; VAS = visual analog scale; QoL = quality of life; HD = high-density stimulation; CRPS = complex regional pain syndrome; PB-SCS = paresthesia-based spinal cord stimulation; PF-SCS = parasthesia-free spinal cord stimulation; SF-36 = Short Form 36; CES-D = Center for Epidemiological Studies–Depression Scale; PGIC = Patient Global Impression of Change; RCT = randomized controlled trial.

Figure 1. PRISMA flowchart for the systematic review.

Table 3. Recommendations for data elements to be included in studies on novel SCS modes for patients with CRPS.

1. Patient-related and CRPS-related data 2. Age 3. Sex 4. BMI 5. CRPS diagnosis confirmed as per IASP Budapest criteria including details of the four domains: sensory, motor, vasomotor, sudomotor 6. Type of trauma that preceeded CRPS 7. Duration of CRPS 8. Analgesic usage 9. Ability to work and or participate in activities important for the patient

Data related to SCS implant and mode

● Stimulation frequency, amplitude or voltage, pulse width, pulse shape  ● Details of the implanted lead in the epidural space and electrode(s) stimulated in relation to vertebral levels

Domains to be assessed at baseline and at serial post-SCS implantation follow-up visits

● Pain-related: NRS, BPI, neuropathic pain score (e.g., DN4) ● Pain-related domains:   ● Functional status (e.g., SF-36, PSQ-3)   ● Psychological status (e.g., PCS, GAD-7, PHQ-9)   ● Physical status (e.g., LEFS)  ○ Analgesic usage  ○ Effect of SCS on CRPS-associated domains  ○ SCS stimulation mode preference  ○ Adverse effects or events related to SCS  ○ Ability to work and or participate in activities important for the patient

SCS = spinal cord stimulation; CRPS = complex regional pain syndrome; BMI = body mass index; IASP = International Association for the Study of Pain; NRS = numerical rating scale; BPI = Brief Pain Inventory; DN4 = Douleur Neuropathique (four questions); SF-36 = Short Form survey (36 items); PSQ-3 = Pain and Sleep Questionnaire (three questions); PCS = Pain Catastrophizing Scale; GAD-7 = Generalized Anxiety Questionnaire (seven questions); PHQ-9 = Patient Health Questionnaire for Depression (nine questions); LEFS = Lower Extremity Function Scale.

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