Exploration of the Association Between White Matter Lesion Burden and Dalfampridine Response in Insidious-Onset Vascular Parkinsonism

An Exploratory Cohort Study to Evaluate Whether White Matter Lesion Burden Correlates With Dalfampridine Response in Insidious-Onset Vascular Parkinsonism and Parkinson-Plus Syndromes

This single-center observational cohort study will be conducted at Tangdu Hospital, Fourth Military Medical University. Patients presenting parkinsonism and poor levodopa response will be enrolled, including insidious-onset vascular parkinsonism (VaP) and Parkinson-plus syndromes (PPS). Within each diagnostic subgroup, participants will receive either dalfampridine 10 mg twice daily for 4 weeks combined with conventional therapy, or conventional therapy alone. Change in Timed Up and Go (TUG) time, gait speed, balance, daily function, and quality of life metrics assessed from baseline to Week 4.

Insidious-onset vascular parkinsonism (VaP) is characterized by typical clinical manifestations including gait impairment, postural instability, poor levodopa responsiveness, and diffuse cerebral white matter lesions (WMLs). Dalfampridine is an agent indicated to manage gait dysfunction among patients diagnosed with multiple sclerosis. This study will collect standardized gait and functional scale assessments in participants with insidious-onset VaP and participants with Parkinson-plus syndromes (PPS).

Single-center observational cohort study performed at Tangdu Hospital, Fourth Military Medical University, Xi'an, China. Parkinsonism and poor levodopa response will be divided into two diagnostic subgroups (VaP, PPS). Each subgroup will receive one of two treatment regimens: dalfampridine 10 mg twice daily for 4 weeks plus conventional therapy, or conventional therapy alone.

Change in Timed Up and Go (TUG) test time,10-meter walking speed, Tinetti scale score, ADL scale score, FES-I score, FOG-Q score, and SF-36 summary scores recorded at baseline and Week 4 among participants with VaP.

Baseline white matter lesion volume will be documented as a baseline clinical characteristic of all enrolled participants.

Inclusion Criteria:

• Age ≥ 18 years
• Clinical diagnosis of insidious-onset vascular parkinsonism or Parkinson-plus syndromes
• Gait, balance, or mobility impairment
• Poor levodopa response (<10% improvement in UPDRS-III after levodopa challenge)
• Ability to complete all study assessments

Exclusion Criteria:

• Seizure disorder or epilepsy
• Multiple sclerosis
• Repeated traumatic brain injury
• Encephalitis, brain tumor, or normal-pressure hydrocephalus
• Severe peripheral neuropathy
• Severe systemic illness or active infection
• Other neurological/psychiatric conditions interfering with assessments