Objective: To identify outcome measures for clinical trials in progressive supranuclear palsy (PSP), the authors determined the time to key motor impairments in a well-defined patient cohort.
Methods: The records of consecutive patients with probable PSP, defined by National Institute of Neurological Disorders and Stroke-Society for Progressive Supranuclear Palsy workshop criteria on first visit to a tertiary care center, were selected for study if the patients were seen regularly at 3- to 6-month intervals, had at least 24 months of care at the Rush movement disorder center, and were originally seen in the movement disorder center before any of the following key motor impairments developed: unintelligible speech, no independent walking, inability to stand unassisted, wheelchair-bound, or recommendation for feeding tube placement. Using standardized criteria from the Unified Parkinson's Disease Rating Scale and Hoehn and Yahr stages taken at each clinic visit, the authors recorded the time that each patient reached the key motor impairments and death. Median months from first symptom onset and from first consultation at the movement disorder center to each motor impairment were derived from Kaplan-Meier curves.
Results: Fifty subjects, mean age at study entry 64.2 years, were followed to death (n = 21, mean duration of surveillance 53.6 months) or in ongoing fashion (n = 29, mean duration of surveillance 46.2 months). Eighty-eight percent of the sample met at least one milestone. The median time from disease onset to the first key motor impairment was 48 months, 24 months after first consultation. The three gait items occurred temporally close, and the authors considered them thereafter as a single milestone, occurring at a median disease duration of 57 months, 34 months after first consultation. Unintelligible speech occurred at a median disease duration of 71 months, median 44 months after first consultation. As a composite end point, speech/gait accounted for 98% of the sample's first key motor impairment. Need for nasogastric tube was rarely the first milestone (8%).
Conclusions: Gait impairment and unintelligible speech are milestones that occur rapidly in PSP and can be monitored with standardized rating scales. The authors suggest that clinical trials use these indices to assess how interventions alter anticipated progression of clinical deterioration in PSP.