ENTF Neuromodulation Yields Reduced Disability After Stroke: An Individual Participant-Level Data Meta-Analysis

Electromagnetic network-targeted field (ENTF) brain stimulation therapy is a promising approach to reduce poststroke disability. Two pilot, randomized, sham-controlled trials showed safety and signals of efficacy. The aim of this study was to perform a pooled analysis with greater statistical power to characterize with precision the effect of ENTF in promoting recovery and reducing disability.

We pooled individual patient-level data from 2 double-blind, randomized, sham-controlled studies, BQ3 (BrainQ3 Trial; Unique identifier: NCT04039178) and EMAGINE 1 (Electromagnetic Field Ischemic Stroke-Novel Subacute Treatment Trial; NCT05044507). Key entry criteria in both trials were (1) 4 to 21 days post-ischemic stroke and (2) Fugl-Meyer assessment-upper extremity score of 10 to 45. For EMAGINE 1, an additional criterion was a study entry modified Rankin Scale (mRS) score of 3 to 4. The primary outcome for this pooled analysis was freedom-from-disability (mRS score, 0-1) at 8 to 12 weeks. Secondary outcomes were level of disability (ordinal mRS score distribution), disability (mRS score) change from entry to 8 to 12 weeks, and 2 focused upper extremity motor end points.

Altogether, 124 patients were included (active n=65; sham n=59). The mean age was 58.2±13.1 years, 31% were female, the study entry Fugl-Meyer assessment-upper extremity score was 25.3 (±10.6), and the therapy started 14.5 (±4.9) days poststroke. The study entry mRS score was 3.9 (±0.36), and 123/124 (99.2%) had a study entry mRS score of 3 to 4. Study entry features were well-balanced across treatment groups. At 8 to 12 weeks, freedom-from-disability was higher with active ENTF than sham stimulation (33.8% versus 11.9%; P=0.005). Ordinal shift across 3 disability strata (mRS score, 0-1, 2, and >2) also favored ENTF (P=0.009). Focused upper extremity motor end points nonsignificantly favored ENTF. Safety analyses showed no device- or procedure-related serious adverse events.

In pooled data from 2 randomized, sham-controlled trials, treatment with ENTF compared with sham for patients with subacute ischemic stroke with moderate-severe study entry disability yielded increased achieved freedom-from-disability, greater disability improvement from study entry, and reduced final disability level. These findings, together with an attractive safety profile, support ENTF as a promising therapy for stroke recovery.