Brainstem Circuit Modulation for PSP

SUMMARY

# Brainstem Circuit Modulation for PSP ## Background and Rationale Progressive Supranuclear Palsy (PSP) is a devastating neurodegenerative tauopathy characterized by selective brainstem circuit dysfunction, particularly affecting the pedunculopontine nucleus (PPN), locus coeruleus, and substantia nigra. Current therapeutic approaches remain largely symptomatic, with limited impact on disease progression or core brainstem-mediated symptoms including gait freezing, postural instability, and oculom

METHODOLOGY NOTES

Phase 1 (Months 1-3): Recruit 60 PSP patients meeting MDS-PSP criteria, age 45-75, disease duration 2-8 years. Conduct comprehensive baseline assessments including PSP Rating Scale, quantitative gait analysis, polysomnography, and 7T MRI with brainstem-specific sequences. Phase 2 (Month 4): Perform stereotactic PPN-DBS implantation using real-time microelectrode recordings and intraoperative imaging guidance. Target coordinates: 5mm lateral, 5mm posterior, 2mm inferior to red nucleus. Implant quadripolar electrodes bilaterally with sensing capabilities. Phase 3 (Months 5-6): Randomize patients 1:1 to active stimulation (20-40 Hz, 60-90 μs pulse width, 2-4V amplitude with burst patterns) versus sham stimulation. Implement double-blind protocol with programmer blinding. Conduct weekly parameter optimization sessions using closed-loop algorithms based on local field potential feedback. Phase 4 (Months 7-18): Monthly assessments including PSP-RS, Unified Parkinson's Disease Rating Scale Pa