Slow Oscillatory Transcranial Direct Current Stimulation for Refractory Focal Epilepsy (so-tDCS-RE)

Slow Oscillatory Transcranial Direct Current Stimulation for Treating Refractory Focal Epilepsy

This pilot study evaluated whether a type of non-invasive brain stimulation called slow-oscillatory transcranial direct current stimulation (so-tDCS) can reduce seizure frequency in patients with drug-resistant focal epilepsy. Ten patients received 14 days of so-tDCS (2 mA, 1 Hz) for 20 minutes twice daily, guided by their individual seizure focus identified by EEG and MRI. Seizure frequency and epileptiform discharges were measured before, during, and up to 8 weeks after treatment. The study also assessed safety and tolerability. Results showed that so-tDCS significantly reduced seizure frequency, with the greatest effect occurring during the first week of treatment, and the benefit was sustained during follow-up. No serious adverse events were reported. These preliminary findings suggest that so-tDCS may be a safe and effective non-invasive option for refractory focal epilepsy, but larger sham-controlled trials are needed to confirm efficacy.

Study Overview

• Status: Completed
• Conditions: Refractory Focal Epilepsy
• Intervention / Treatment: Device: Slow-oscillatory transcranial direct current stimulation (so-tDCS)

Detailed Description

tudy Design This was a prospective, open-label, single-arm pilot study conducted at the First Hospital of Hebei Medical University, China. Ten patients with refractory focal epilepsy (ILAE 2017 criteria) were enrolled. All patients completed the full treatment and follow-up protocol.

Participants Inclusion criteria: age 6-60 years, focal epilepsy, failed ≥2 anti-seizure medications, stable medication for ≥4 weeks, ≥2 seizures during 4-week baseline. Exclusion criteria: psychogenic nonepileptic seizures, progressive neurological disease, implanted electronic devices, pregnancy/lactation.

Intervention Slow-oscillatory tDCS (so-tDCS) was delivered using a constant-current stimulator (Hypnos Tech, China). The cathode was placed over the neuroimaging-defined epileptogenic zone (using MRI, FDG-PET, MEG, and scalp EEG). The reference anode was placed at FP1 or FP2 (contralateral). Stimulation parameters: 1 Hz sinusoidal oscillatory current, 2 mA peak-to-peak, delivered for 20 minutes per session, twice daily, with a 20-minute interval between sessions, for 14 consecutive days (total 40 minutes/day). Each session included a 20-second linear ramp-up and ramp-down. Sponge electrodes (13.68 cm²) soaked in 0.9% saline were used.

Outcome Measures Primary outcome: Percentage change in seizure frequency during treatment (14 days) and follow-up (8 weeks) compared with baseline.

Secondary outcomes: Change in interictal epileptiform discharges (IEDs) per hour on long-term EEG; change in alpha power (8-13 Hz) at Pz, CZ, P3, and C3 electrodes; safety and tolerability (adverse events); exploratory analysis of etiology (e.g., encephalomalacia vs. FCD) and treatment response.

Assessments Seizure diaries were kept daily. Long-term EEG (~16 hours) was recorded at baseline, post-treatment (week 2), and follow-up (week 10). Epileptiform discharges were quantified by two blinded electroencephalographers. EEG spectral analysis (FFT) was performed for theta, alpha, beta, and gamma bands.

Statistical Analysis Wilcoxon signed-rank test was used for seizure frequency changes. Repeated-measures ANOVA was used for IEDs. For alpha power, Wilcoxon signed-rank test with Bonferroni correction (12 electrode sites, α=0.00417) was applied. Effect sizes (Cliff's delta, Cohen's d) were calculated where appropriate. No imputation was made for missing data (none occurred).

Results Summary Seizure frequency significantly decreased during treatment (median reduction 95.65%, p=0.0020) and follow-up (median reduction 76.35%, p=0.0122). Six of ten patients achieved ≥78% reduction. IED frequency decreased significantly (p=0.0434). Alpha power increased significantly at Pz, CZ, and P3 (Bonferroni-corrected). The most pronounced seizure reduction occurred in the first week. No serious adverse events were reported; only mild transient skin itching/erythema in two adults, which resolved without treatment.

Limitations Small sample size, open-label design (no sham control), and heterogeneity in etiologies limit generalizability. The results are hypothesis-generating; sham-controlled randomized trials are needed to confirm efficacy.

Conclusion This pilot study provides preliminary evidence that so-tDCS is safe, well-tolerated, and associated with seizure reduction in refractory focal epilepsy, with a rapid onset and sustained effect. Further studies with sham control and larger cohorts are warranted.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • The First Hospital of Hebei Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria were established as follows:(1)a confirmed diagnosis of focal-onset seizures, with or without focal-to-bilateral tonic-clonic evolution, according to the ILAE 2017 classification; (2)a disease duration of at least 2 years; (3)pharmacoresistance, defined as failure of adequately tried, appropriately chosen, and well-tolerated trials of at least two antiseizure medications (ASMs); (4)a stable ASM regimen for at least 4 weeks prior to baseline with agreement to maintain the same regimen throughout the study; (5)concurrent use of one to five ASMs; (6)at least two seizures during the 4-week baseline observation period.

Exclusion criteria included:(1) psychogenic nonepileptic seizures; (2) progressive neurological or systemic disorders other than epilepsy; (3) pregnancy or breastfeeding; (4) substance abuse; (5) the presence of implanted electrical medical devices.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: so-tDCS; Participants received 14 days of slow-oscillatory transcranial direct current stimulation (so-tDCS) over the neuroimaging-defined epileptogenic zone (cathode), with reference anode at FP1/FP2. Stimulation: 1 Hz, 2 mA, two 20-minute sessions per day (20-minute interval), for 14 consecutive days.

Device: Slow-oscillatory transcranial direct current stimulation (so-tDCS); 1 Hz sinusoidal oscillatory current, 2 mA peak-to-peak, delivered via sponge electrodes (13.68 cm²) soaked in 0.9% saline. Cathode placed over individual epileptogenic zone (defined by MRI, FDG-PET, MEG, and scalp EEG). Reference anode placed at FP1 or FP2 (contralateral). Each session: 20 minutes with 20-second ramp-up/ramp-down. Two sessions per day, separated by a 20-minute rest period, for 14 consecutive days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in seizure frequency	Percentage change in weekly seizure frequency from baseline to the end of the 2-week treatment period, and to the end of the 8-week follow-up period.	Baseline (4 weeks), during treatment (weeks 1-2), and follow-up (weeks 3-10)

Collaborators and Investigators

• Sponsor: The First Hospital of Hebei Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2024
• Primary Completion (Actual): April 30, 2024
• Study Completion (Actual): October 31, 2024

Study Registration Dates

• First Submitted: June 29, 2026
• First Submitted That Met QC Criteria: June 29, 2026
• First Posted (Actual): July 6, 2026

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: June 29, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Epilepsies, Partial
• Other Study ID Numbers: so-tDCS-RE-2024; 2022YFC3600500 (Other Grant/Funding Number: the National Key Research and Development Program of China)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No