Table 2.

Summary of clinical trials from the last 10 years (2013–2022) investigating motor cortex stimulation (MCS) for various chronic pain conditions

Study	Country	Study design	MCS type	Sample size	Chronic pain condition	Main results	Adverse events
Hamani 2021 [73]	Brazil	RCT	Epidural MCS	18	Trigeminal neuropathic pain (n = 3); CPSP (n = 4); brachial plexus avulsion (n = 6); phantom limb pain (n = 3); CRPS (n = 2)	39% of patients adequately responded to treatment in 1-year follow-up with a minimum 2-point or 30% reduction in NRS scores.	Infection (n = 1), pseudo-seizures (n = 1), intraoperative seizure (n = 1), device failure (n = 1), discomfort neck (n = 6), incision hyperemia (n = 3)
Sokal 2019 [74]	Poland	Open-label single-arm study	Epidural MCS	6	Thalamic pain (n = 3), trigeminal neuralgia (n = 3)	In 5 patients, burst MCS was more effective than tonic mode.	N/A
Henssen 2018 [75]	Netherlands	Open-label single-arm study	Epidural MCS	18	CPSP (n = 7); trigeminal neuralgia (n = 3); trigeminal neuropathic pain (n = 2); idiopathic facial pain (n = 2); post-surgical pain (n = 1); brachial plexus avulsion (n = 1); phantom limb pain (n = 1)	Statistically significant improvement in VAS in 3-year follow-up; successful treatment in 38.9% of patients; benefits only in patients with CNS lesion.	Infection (n = 3); intraoperative seizures (n = 1); device failure (n = 1)
Tanei 2018 [76]	Japan	Retrospective study	Epidural MCS (vs SCS)	SCS group: 35; MCS group: 15	MSC group: CPSP (n = 9); trigeminal neuropathic pain (n =2); SCI (n = 2); multiple sclerosis (n = 1); brachial plexus avulsion (n = 1); SCS group: CPSP (n = 17); FBSS (n = 7); SCI (n = 4); peripheral neuropathy (n = 3); CRPS (n = 1); other causes (n = 3)	53.3% of patients demonstrated a beneficial effect of MCS 12-month post surgery; VAS at 1-month post-surgery may be a predictive factor of the long-term effects (both MCS and SCS).	N/A
Zhang 2018 [77]	China	Retrospective study	Epidural MCS, subdural MCS	16	CPSP	Statistically significant mean VAS and NPSI reduction after a 5.3-year mean follow-up.	N/A
Ivanishvili 2017 [78]	Canada	RCT	N/A	6	CPSP (n = 3); atypical facial pain (n = 3)	4 patients adequately responded to treatment; cyclization of MCS was not inferior to constant MCS with regards to pain tolerability; the subjects preferred cyclized MCS in program 15min ON/15min.	N/A
Zhang 2017 [64]	China	Retrospective study	Epidural MCS, subdural MCS	16	CPSP	Significant pain reduction (mean follow-up: 28 months); a significant association between preoperative rTMS and effective outcomes was demonstrated.	Intraoperative seizures (n = 2), subdural effusion (n = 1), electrode shift (n = 1)
Rasche 2016 [79]	Germany	Open-label single-arm study	Epidural MCS	36	Trigeminal neuropathic pain	26 patients demonstrated statistically significant pain reduction in VAS 5.6 years after MCS.	Wound infections (n = 4), device failure (n = 2), seizures and epidural scar (n = 1)
Kolodziej 2016 [80]	Germany	Retrospective study	Epidural MCS	20	Central pain (n = 8), deafferentation pain (n = 3), and neuropathic trigeminal pain (n = 9)	95% of patients demonstrated at least satisfactory pain control (at least 60% pain relief).	Device failure (n = 3), wound infection (n = 1), epidural hematoma (n = 1)
Radic 2015 [81]	Canada	RCT	Epidural MCS	12	Brachial plexus avulsion (n = 6); phantom limb pain (n = 2); CRPS (n = 3); deafferentation pain (n = 1)	Trial suspended due to adverse effects, lack of significant change in VAS, no significant changes in other measured outcomes.	Device failure (n = 1); infection (n = 1); focal motor seizures (n = 2); anxiety following seizure (n = 1); panic attacks (n = 1)
Sokal 2015 [82]	Poland	Retrospective study	Epidural MCS	14	CPSP (n = 7), atypical facial pain (n = 2), brachial plexus avulsion (n = 3), phantom pain, (n = 1), pain in syringomyelia (n = 1)	Over 80% pain reduction in 31% of the patients in the long term; 50–80% pain reduction in 23% of the patients in the long term; the highest efficacy in post-stroke or post-hemorrhagic thalamic pain.	Transient seizures (n = 3); wound infection (n = 1); device failure (n = 1)
Isagulyan 2015 [83]	Russia	Open-label single-arm study	Epidural MCS + pre-op rTMS	20	CPSP (n = 4), atypical facial pain (n = 4), phantom limb pain (n = 3), brachial plexus injury (n = 4), spinal cord injury (n = 3), CRPS (n = 1), multiple sclerosis (n = 1)	14 patients adequately responded to MCS with a reduction in the pain intensity ranging from 25 to 60% after a mean follow-up of 49.3 months; the effect of pre-op rTMS was not statistically significant.	Device failure (n = 1); infection (n = 2)
Im 2015 [84]	Korea	Retrospective study	Epidural MCS	21	CPSP (n = 10), central pain after SCI (n = 6); peripheral neuropathic pain (n = 5)	76.2% of patients achieved treatment success after 53-month follow-up; only the patients with poststroke pain and peripheral neuropathic pain achieved significant pain reduction (>30% pain relief).	N/A
Andre-Obadia 2014 [85]	France	RCT	Epidural MCS + pre-op rTMS	20	CPSP (n = 11); trigeminal neuropathy (n = 4); cervical spinal pain (n =2); brachial plexus avulsion (n = 2); ulnar nerve injury (n = 1)	10 patients achieved long-term (6-year follow-up) benefits in pain reduction.	N/A
Sachs 2014 [86]	Canada	Retrospective study	Epidural MCS	14	Trigeminal neuropathic pain (n = 7); phantom limb pain (n = 3); CPSP (n = 1); spinal cord injury (n = 1); medullary cavernous malformation (n = 1); facial hemangiopericytoma (n = 1)	Only 2 patients experienced >50% pain reduction (mean follow-up: 55.5 weeks).	Infection (n = 2); intraoperative seizures (n = 3)
Buchanan 2014 [65]	USA	Retrospective study	Epidural MCS, subdural MCS	8	CPSP (n = 2); facial pain (n = 5); phantom limb pain (n = 1)	Statistically significant decrease of mean VAS score at 3-month follow-up.	Transient seizures (n = 1)
Delavallee 2014 [87]	Belgium	Open-label single-arm study	Subdural MCS	18	Trigeminal neuropathic pain (n = 7); CPSP (n = 3); brachial plexus avulsion (n = 2); C2 avulsion (n = 2); SCI (n = 1); cubital nerve injury (n = 1); CRPS (n = 1); phantom limb pain (n = 1)	77.7% of the patients achieved >50% pain relief at 3-year follow-up.	Transient seizures (n = 4); superficial wound infections (n = 4); subdural scar (n = 1)

CPSP central post-stroke pain, CRPS complex regional pain syndrome, FBSS failed back surgery syndrome, N/A not available, NPSI neuropathic pain symptom inventory, NRS numerical pain rating scale, RCT randomized controlled trial, SCI spinal cord injury, VAS visual analogue scale, Vc ventralis caudalis