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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/15752

Title: Natural history of motor symptoms in Parkinson’s disease and the long-duration response to levodopa
Authors: Roberto, Cilia
Cereda, Emanuele
Akpalu, Albert
Sarfo, Fred Stephen
Cham, Momodou
Laryea, Ruth
Obese, Vida
Oppon, Kenneth
Del Sorbo, Francesca
Bonvegna, Salvatore
Lena Zecchinelli, Anna
Pezzoli, Gianni
Keywords: Parkinson’s disease
long-term response
motor fluctuations
Issue Date: Jul-2020
Publisher: Brain
Citation: Brain, 143(8):2490-2501
Abstract: The natural pattern of progression of Parkinson’s disease is largely unknown because patients are conventionally followed on treatment. As Parkinson’s disease progresses, the true magnitude of the long-duration response to levodopa remains unknown, because it can only be estimated indirectly in treated patients. We aimed to describe the natural course of motor symptoms by assessing the natural OFF in consecutive Parkinson’s disease patients never exposed to treatment (drug-naı¨ve), and to investigate the effects of daily levodopa on the progression of motor disability in the OFF medication state over a 2-year period. In this prospective naturalistic study in sub-Saharan Africa, 30 Parkinson’s disease patients (age at onset 58± 14 years, disease duration 7 ± 4 years) began levodopa monotherapy and were prospectively assessed using the Unified Parkinson’s disease Rating Scale (UPDRS). Data were collected at baseline, at 1-year and 2-years follow-up. First-ever levodopa intake induced a significant improvement in motor symptoms (natural OFF versus ON state UPDRS-III 41.9± 15.9 versus 26.8± 15.1, respectively; P50.001). At 1-year follow-up, OFF state UPDRS-III score after overnight withdrawal of levodopa was considerably lower than natural OFF (26.5± 14.9; P50 .001). This effect was not modified by disease duration. At the 2-year follow-up, motor signs after overnight OFF (30.2± 14.2) were still 30% milder than natural OFF (P = 0.001). The ON state UPDRS-III at the first-ever levodopa challenge was similar to the overnight OFF score at 1-year follow-up and the two conditions were correlated (r = 0.72, P50.001). Compared to the natural progression of motor disability, levodopa treatment resulted in a 31% lower annual decline in UPDRS-III scores in the OFF state (3.33 versus 2.30 points/year) with a lower model’s variance explained by disease duration (67% versus 36%). Using the equation regressed on pretreatment data, we predicted the natural OFF at 1-year and 2-year follow-up visits and estimated that the magnitude of the long-duration response to levodopa ranged between 60% and 65% of total motor benefit provided by levodopa, independently of disease duration (P = 0.13). Although levodopa therapy was associated with motor fluctuations, overnight OFF disability during levodopa was invariably less severe than the natural course of the disease, independently of disease duration. The same applies to the yearly decline in UPDRS-III scores in the OFF state. Further research is needed to clarify the mechanisms underlying the long-duration response to levodopa in Parkinson’s disease. Understanding the natural course of Parkinson’s disease and the long-duration response to levodopa may help to develop therapeutic strategies increasing its magnitude to improve patient quality of life and to better interpret the outcome of randomized clinical trials on disease-modifying therapies that still rely on the overnight OFF to define Parkinson’s disease progression.
Description: This article is published by Brain and is also available at doi:10.1093/brain/awaa181
URI: 10.1093/brain/awaa181
Appears in Collections:College of Health Sciences

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