Objective: This study aimed to evaluate the safety and efficacy of Electrosonic Stimulation (ESStim) delivered in conjunction with physical therapy (PT) in Parkinson’s disease (PD).

Background: PD is the second most prevalent neurodegenerative disorder worldwide. Motor disabilities, including postural instability and gait impairment, remain inadequately addressed by pharmacological therapy. ESStim is a non-invasive neuromodulation technique combining transcranial ultrasound and transcranial direct current stimulation. In a prior Phase I randomized, double-blind, sham-controlled trial in 18 patients with PD and postural instability, ESStim plus PT produced greater improvement in UPDRS III than Sham plus PT, with benefits sustained through 6 weeks. Here, we evaluated a longer treatment course in a larger cohort.

Method: In a single-center, randomized, double-blind, sham-controlled Phase II trial, 40 PD participants reporting postural instability were assigned to Active ESStim (n=20) or Sham (n=20). Participants received 14 stimulation sessions targeting the primary motor cortex over 4 weeks (20 min/session), concurrent with 10 PT sessions emphasizing gait and balance training. Follow-up occurred at ~1, 2, 4, 6, and 8 weeks post-treatment. UPDRS III scores were assessed during the levodopa “ON” state. Safety was assessed via adverse event monitoring, EEG, neurological examination, and cognitive testing (SCOPA-Cog, SPMSQ).

Results: All 40 participants completed the intervention. Stimulation resulted in no serious adverse events. Minor expected side effects were transient. The mean baseline UPDRS III score was 15.3. Improvement in UPDRS III differed between groups over time (p<0.05; two-way ANOVA). Compared with baseline, UPDRS III scores improved by 22% in the Active group vs 8% in the Sham group during the 4-week treatment period, and by 25% in the Active group vs a 3% worsening in Sham across the entire 12-week trial period.

Conclusion: ESStim combined with PT was safe and produced sustained motor improvement compared with Sham plus PT, confirming and extending prior Phase I findings in a longer 12-week randomized trial. A multicenter pivotal trial is planned.

References: Noninvasive Electrosonic Brain Stimulation for Motor, Balance, and Gait Improvement in Parkinson’s Disease. Ramos-Estebanez et al. NANS Annual Meeting, Las Vegas, USA 2026

Novel methods of transcranial stimulation: electrosonic stimulation. Wagner T, Dipietro L. In: Krames ES, Peckham PH, Rezai AR, editors. Neuromodulation. Cambridge: Academic Press. 2018

Funding: Work reported in this publication was supported in part by the National Institutes of Health NINDS (Award Number R44NS110237). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/noninvasive-electrosonic-brain-stimulation-for-parkinsons-disease-results-from-a-phase-ii-trial/