Motor Score of the Unified Parkinson Disease Rating Scale as a Good Predictor of Lewy Body–Associated Neuronal Loss in the Substantia Nigra

Abstract

BACKGROUND: How well the motor symptoms assessed by the motor section of the Unified Parkinson Disease Rating Scale (UPDRS3) reflect the neuronal loss observed in the substantia nigra is not known. OBJECTIVE: To study the relationships among the motor symptoms assessed by the UPDRS3, Lewy body-associated neuronal loss in the substantia nigra, and duration of disease. DESIGN: Longitudinal, prospective, clinicopathological study. SETTING: Long-term care facility of a university hospital. PATIENTS: Eighteen elderly patients with a parkinsonian syndrome, studied prospectively but selected post mortem on the basis of the presence of Lewy bodies, and 5 age-matched control subjects. METHODS: One map of a section of the substantia nigra, indicating the location of all the nucleolated neuronal profiles, was drawn for each case. Neuronal density was estimated using a tessellation method. The relationship between time and neuronal loss and between neuronal loss and motor symptoms (assessed by the UPDRS3) was studied by means of regression analysis, using linear and exponential models. RESULTS: The neuronal density was linearly linked with the UPDRS3 score (r = -0.83 [P<.001]). Each point added to the UPDRS3 score corresponded to an estimated loss of 25 neurons/mm(3). The density of neuronal profiles in the substantia nigra decreased exponentially with time (r = -0.73 [P<.001]). Extrapolation of the curve suggested a presymptomatic phase of 5 years. CONCLUSION: The UPDRS3 score is linearly linked to neuronal density, which, in Lewy body diseases, decreases exponentially with time at a similar pace in this series of elderly patients and in the younger patients described in the literature.