A randomized controlled trial to evaluate the effectiveness and safety of electro acupuncture and transcranial direct current stimulation with computerized cognitive rehabilitation in patients with vascular cognitive impairment.

BACKGROUND: Vascular cognitive impairment (VCI) refers to all cognitive disorders caused by cerebrovascular disorders. For the treatment, many types of pharmacologic and nonpharmacologic treatments are used but their underlying mechanisms and effects are unclear. Regarding nonpharmacologic treatment, electroacupuncture (EA), transcranial direct current stimulation (tDCS), and computerized cognitive rehabilitation treatment (CCRT) are effective. Here, we report the protocol for a randomized controlled trial of the effect and safety of combination therapy of EA or tDCS and CCRT in patients with VCI. METHODS: This study will be a prospective, outcome assessor-blinded, parallel-arm, randomized controlled clinical trial. Participants with cognitive impairment caused by stroke after 3 months of onset (n = 45) will be randomly assigned to a CCRT, combination therapy with EA and computerized cognitive rehabilitation treatment, or combination therapy with tDCS and computerized cognitive rehabilitation treatment group. All groups will receive treatment 3 times per week for 8 weeks, giving a total of 24 treatments. The CCRT group will perform a training task like shopping, calculating, and others and involving computerized cognitive assessment and brain training system (RehaCom) for 30 minutes. The combination therapy with EA and computerized cognitive rehabilitation treatment group will receive EA using 8 acupuncture points - baekhoe, sinjeong, both sides of pungji, 4 sites of sishencong - and will be applied using an EA stimulator and receive CCRT for 30 minutes at the same time. The combination therapy with tDCS and computerized cognitive rehabilitation treatment group will receive tDCS treatment and receive CCRT for 30 minutes at the same time. The primary outcome will be evaluated using the Lowenstein occupational therapy cognitive assessment, while other scales assessing walking ability, activities of daily living, and quality of life are considered secondary outcome measures. Outcomes will be evaluated before intervention, at the end of intervention 8 weeks after the first intervention, and 4 weeks after completion of the intervention program. DISCUSSION: This study aims to examine the effect and safety of combination therapy with EA or tDCS and CCRT in patients with VCI. This study can be useful in developing new treatment technologies using collaborative research with combined traditional Korean and conventional medicines. TRIAL REGISTRATION: This trial has been registered with cris.nih.go.kr (registration number, KCT 0003644 Registered 01 April 2019, http://cris.nih.go.kr).

Regulation of gene expression after combined scalp acupuncture and transcranial magnetic stimulation in middle cerebral artery occlusion mice.

BACKGROUND: The effect of combined repetitive transcranial magnetic stimulation (rTMS) and scalp acupuncture stimulation (SAS) on middle cerebral artery occlusion (MCAO) mice has not yet been reported. The regulation of gene expression after combined stimulation remains unclear. OBJECTIVE: To analyze gene expression patterns through ribonucleic acid (RNA) sequencing. METHODS: Thirty-six 8-weeks-old C57BL/6J male mice weighing 50-60 grams were used for this experiment. The MCAO was induced with 60-min occlusion and subsequent reperfusion of the middle cerebral artery. Experimental mice were randomly assigned to four groups, with nine mice in each group, as follows: control group (no treatment), SAS group (10 minutes SAS), rTMS group (1 Hz rTMS), and combined group (1 Hz rTMS and SAS). Stimulation was performed from the 3rd day to the 7th day after the induction of MCAO. All mice were sacrificed, and brain tissues were taken from the motor area of the MCAO lesion. We analyzed their gene expression profiles using RNA sequencing technology. RESULTS: After stimulation, the grip strength increased in the SAS and rTMS group compared to the control and combined group. The nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) was the key up-regulated protein in the SAS group while src homologus and collagene gene (SHC) and p90 ribosomal protein S6 kinases (p90RSK) were key up-regulated proteins in the rTMS group. However, the C-terminal src kinase-homologous kinase (CHK) was down-regulated whereas p90RSK was up-regulated in the combined group based on the RNA sequencing analysis. CONCLUSIONS: Each stimulation method showed different patterns with neurotrophin signaling pathway including NFκB, SHC, p90RSK, and CHK. These can be used in further mechanistic studies about gene expression related to neurorecovery.

Synergistic Effects of Scalp Acupuncture and Repetitive Transcranial Magnetic Stimulation on Cerebral Infarction: A Randomized Controlled Pilot Trial.

This study investigated the synergistic effects of scalp acupuncture (SA) and repetitive transcranial magnetic stimulation (rTMS), known to be effective for cerebral infarction. This outcome-assessor-blinded, randomized controlled clinical trial included a per-protocol analysis to compare the efficacy of SA and electromagnetic convergence stimulation (SAEM-CS) and single or no stimulation. The trial was conducted with 42 cerebral infarction patients (control group, 12; SA group, 11; rTMS group, 8; SAEM-CS group, 11). All patient groups underwent two sessions of CSRT per day. SA, rTMS, and SAEM-CS were conducted once per day, 5 days per week, for 3 weeks. The primary outcome was evaluated using the Fugl-Mayer assessment (FMA). FMA Upper Extremity, FMA total, MBI, and FIM scores significantly increased in the rTMS group compared with the control group. Additionally, FMA Upper Extremity, FMA total, MBI and FIM scores significantly increased in the rTMS group compared with the SAEM-CS group. However, there were no significant changes in the SA or SAEM-CS groups. In conclusion, low-frequency rTMS in the contralesional hemisphere may have long-term therapeutic effects on upper extremity motor function recovery and improvements in activities of daily living. SAEM-CS did not show positive synergistic effects of SA and rTMS.

Scalp acupuncture and electromagnetic convergence stimulation for patients with cerebral infarction: study protocol for a randomized controlled trial.

BACKGROUND: Scalp acupuncture (SA) and repetitive transcranial magnetic stimulation (rTMS) are effective for treating cerebral infarction. This study aims to examine the efficacy and safety of SA and electromagnetic convergence stimulation (SAEM-CS), which was developed through collaboration between conventional medical physicians and doctors who practice traditional Korean medicine. SAEM-CS was designed to improve function in patients with cerebral infarction, compared to the improvement after conventional stroke rehabilitation, SA, and rTMS therapeutic approaches. METHODS/DESIGN: This study is a prospective, outcome assessor-blinded, randomized controlled clinical trial with a 1:1:1:1 allocation ratio. Participants with motion or sensory disabilities caused by a first-time cerebral infarction (n = 60) that had occurred within 1 month of the study onset will be randomly assigned to control, SA, rTMS, or SAEM-CS groups. All groups will receive two sessions of conventional rehabilitation treatment per day. The SA group will receive SA on the upper limb area of MS6 and MS7 (at the lesional hemisphere) for 20 min, the rTMS group will receive low-frequency rTMS (LF-rTMS) treatment on the hot spot of the M1 region (motor cortex at the contralesional hemisphere) for 20 min, and the SAEM-CS group will receive LF-rTMS over the contralesional M1 region hot spot while receiving simultaneous SA stimulation on the lesional upper limb area of MS6 and MS7 for 20 min. SA, rTMS, and SAEM-CS treatments will be conducted once/day, 5 days/week (excluding Saturdays and Sundays) for 3 weeks, for a total of 15 sessions. The primary outcome will be evaluated using the Fugl-Meyer Assessment, while other scales assessing cognitive function, activities of daily living, walking, quality of life, and stroke severity are considered secondary outcome measures. Outcome measurements will be conducted at baseline (before intervention), 3 weeks after the first intervention (end of intervention), and 4 weeks after intervention completion. DISCUSSION: This study aims to explore the efficacy and safety of SAEM-CS on cerebral infarction. Collaborative research combined traditional Korean and conventional medicines, which can be useful in developing new treatment technologies. TRIAL REGISTRATION: KCT0001768 . Registered on 14 January 2016.