Long Duration Response in Parkinson's Disease: Levodopa Revisited

Werner Poewe; Alberto J. Espay


Brain. 2020;143(8):2332-2335. 

In This Article

On the Severity and Progression of Motor Features in Untreated Parkinson's Disease

Previous attempts to characterize the 'natural history' of Parkinson's disease have relied on data from the pre-levodopa era (Poewe and Wenning, 1998), most notably in the seminal study by Margaret 'Peggy' Hoehn and Melvin Yahr describing the progression and mortality in a cohort of patients with 'primary parkinsonism' followed at the Columbia-Presbyterian Medical Centre in New York (Hoehn and Yahr, 1967). Using their now famous Hoehn and Yahr staging system for Parkinson's disease severity, they found that almost one-third of 271 subjects never treated by yet-unavailable levodopa had become severely disabled (Hoehn and Yahr stages 4 or 5) or had died after only 5 years of disease duration; this figure rose beyond 80% at 15 years. Although these data may have overestimated the malignancy of pre-levodopa Parkinson's disease progression by including patients who today would have been diagnosed with other parkinsonian syndromes such as multiple system atrophy or progressive supranuclear palsy, the study by Cilia and colleagues seems to confirm the conclusions of Hoehn and Yahr. Using current diagnostic criteria in patients with a mean of 7 years after symptom onset minimized chances of diagnostic misclassification. This untreated 'modern pre-levodopa era' cohort had a mean Hoehn and Yahr stage of 3 at baseline, with 40% of patients already exhibiting postural instability and falls (Cilia etal., 2020).

Using linear regression to quantify the contribution of disease duration to worsening motor function and model progression of UPDRS scores during the untreated period, Cilia and colleagues calculated a progression rate of UPDRS motor scores of 3.3 points per year. This is just above the annual decline of 2.4 points/year in the motor section (part 3) of the revised MDS-UPDRS scale, calculated from 5-year data of initially naïve but subsequently treated patients enrolled in the Parkinson's Progression Markers Initiative study (Holden etal., 2018).