Temporal patterns of neurostimulation efficacy in drug-resistant epilepsy: A systematic review and meta-analysis

To systematically evaluate the temporal efficacy trajectories and relative performance of four neurostimulation modalities (open-loop Vagus Nerve Stimulation [ol-VNS], closed-loop VNS [cl-VNS], Deep Brain Stimulation [DBS], and Responsive Neurostimulation [RNS]) in patients with drug-resistant epilepsy (DRE).

Following PRISMA guidelines, PubMed, Cochrane Library, and Web of Science were searched for studies published during the modern neuromodulation era (2014-2024). We included original studies of patients without prior resective surgery who received single-device implantation. Data were mapped into four standardized follow-up windows (3, 6, 12-18, and ≥21 months). Pooled responder rates (RRs, ≥50% seizure reduction) were calculated using a random-effects model. A mixed-effects meta-regression was conducted to explore the interaction between device modality and time.

A total of 94 unique cohorts were included. Overall RRs demonstrated a robust, time-dependent improvement: 38.7% (95% CI: 29.9%-48.4%) at 3 months, 48.2% (95% CI: 42.3%-54.1%) at 6 months, 59.3% (95% CI: 56.2%-62.2%) at 12-18 months and peaking at 61.8% (95% CI: 57.6%-65.7%) at ≥ 21 months. Meta-regression (Q_M = 96.3, p < 0.0001) confirmed a highly significant main effect for follow-up duration. While numerical differences existed among devices (with cl-VNS, DBS, and RNS showing higher overall efficacy baselines compared to ol-VNS), the interaction terms between device type and follow-up duration were universally non-significant (all p > 0.05), indicating that the current data do not provide statistical evidence of diverging temporal trajectories across modalities.

Across all modalities, neurostimulation produced a robust, time-dependent improvement in responder rates, with progressive gains consolidating over 1-2 years. This temporal pattern is consistent with the hypothesis of delayed network remodeling, though the present data cannot confirm a shared mechanism. Numerical differences in baseline responder rates across devices are more likely attributable to patient selection and indication bias than to intrinsic hardware superiority.