Slow Oscillatory Transcranial Direct Current Stimulation for Refractory Focal Epilepsy

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.

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.

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.