Transcranial Pulse Stimulation in Parkinson's Disease: A Systematic Review

Transcranial pulse stimulation (TPS) is an emerging ultrasound-based neuromodulation technique with potential applications in Parkinson's disease (PD). This systematic review evaluated its clinical efficacy, neurophysiological and neuroimaging effects, safety, and certainty of evidence.

PubMed/MEDLINE, Embase, and Scopus were systematically searched for clinical studies investigating TPS in adults with idiopathic PD. Motor, non-motor, cognitive, neurophysiological, neuroimaging, and safety outcomes were narratively synthesized because of methodological heterogeneity. Risk of bias was assessed, and evidence certainty was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.

Four studies involving 80 participants were included: two sham-controlled studies, one prospective open-label pilot study, and one retrospective uncontrolled study. Uncontrolled studies reported improvements in motor function, non-motor symptoms, cognition, mood, and quality of life. However, a randomized double-blind crossover trial demonstrated no superiority of active TPS over sham for global motor scores (MDS-UPDRS Part III). Significant improvements in left-hand manual dexterity persisted for one month and were accompanied by sensorimotor activation and white-matter changes. A single-session study reported immediate resting-tremor reduction, although sustained superiority over sham remained uncertain. Electroencephalographic findings suggested cortical oscillatory modulation. No serious treatment-related adverse events were reported. Evidence certainty ranged from moderate to very low.

TPS shows preliminary potential to modulate sensorimotor networks and improve selected motor outcomes in PD. However, evidence remains insufficient to establish overall clinical efficacy. Larger, rigorously controlled trials are required to determine sustained benefits, optimal stimulation protocols, and long-term safety.