Naveed Malek1, Sofia Kanavou2, Michael A Lawton2, Vanessa Pitz3, Katherine A Grosset3, Nin Bajaj4, Roger A Barker5, Yoav Ben-Shlomo2, David J Burn6, Tom Foltynie7, John Hardy8, Nigel M Williams9, Nicholas Wood10, Huw R Morris11, Donald G Grosset3. 1. Department of Neurology, East Suffolk and North Essex NHS Foundation Trust, Ipswich, UK. Electronic address: nmalek@nhs.net. 2. School of Social and Community Medicine, University of Bristol, Bristol, UK. 3. Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UK. 4. Department of Neurology, University of Nottingham, UK. 5. Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, Cambridge, UK. 6. Faculty of Medical Sciences, University of Newcastle, Newcastle upon Tyne, UK. 7. Department of Clinical and Movement Neurosciences, UCL Institute of Neurology, London, UK. 8. Reta Lila Weston Laboratories, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. 9. Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK. 10. Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. 11. Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK.
Abstract
BACKGROUND: L-dopa responsiveness in Parkinson's disease (PD) varies, but the clinical correlates and significance of this are ill-defined. METHODS: Patients were assessed before and after their usual morning L-dopa dose, using the MDS Unified PD Rating Scale Part 3 (MDS UPDRS 3), and rated as definite responders (≥24.5% improvement) or limited responders (<24.5%). RESULTS: 1007 cases, mean age 66.1 years (SD 9.1) at diagnosis, were assessed 3.4 (SD 0.9) years after diagnosis. The L-dopa response was definite in 614 cases (61.0%), median reduction in MDS UPDRS 3 scores was 42.0%, (IQR 33.3, 53.1), and was limited in 393 cases (39.0%), median reduction in MDS UPDRS 3 scores 11.5% (IQR 4.3, 18.2). Definite responders were younger (66.3 years at study entry, SD 9.3) than limited responders (69.2 years, SD 8.4, p < 0.001). The MDS UPDRS 3 score at study entry in definite responders (21.0, SD 10.5) was significantly lower than in limited responders (24.7, SD 13.4, p < 0.001). The MDS UPDRS 3 increase over 18 months was less in definite responders at 3.0 (SD 10.4), compared to limited responders (6.4, SD 11.0, p < 0.001). The levodopa equivalent daily dose (LEDD) was not significantly different at study entry (definite responders 317 mg, SD 199, vs limited responders 305 mg, SD 191, p = 0.53). However, LEDD was significantly higher at the time of the L-dopa challenge test in definite responders (541 mg, SD 293) compared to limited responders (485 mg, SD 215, p = 0.01). Responsiveness to L-dopa was unaffected by the challenge test dose (p = 0.54). CONCLUSIONS: The main determinants of variation in the L-dopa response in early PD are age and motor severity. A limited L-dopa response is associated with faster motor progression.
BACKGROUND:L-dopa responsiveness in Parkinson's disease (PD) varies, but the clinical correlates and significance of this are ill-defined. METHODS:Patients were assessed before and after their usual morning L-dopa dose, using the MDS Unified PD Rating Scale Part 3 (MDS UPDRS 3), and rated as definite responders (≥24.5% improvement) or limited responders (<24.5%). RESULTS: 1007 cases, mean age 66.1 years (SD 9.1) at diagnosis, were assessed 3.4 (SD 0.9) years after diagnosis. The L-dopa response was definite in 614 cases (61.0%), median reduction in MDS UPDRS 3 scores was 42.0%, (IQR 33.3, 53.1), and was limited in 393 cases (39.0%), median reduction in MDS UPDRS 3 scores 11.5% (IQR 4.3, 18.2). Definite responders were younger (66.3 years at study entry, SD 9.3) than limited responders (69.2 years, SD 8.4, p < 0.001). The MDS UPDRS 3 score at study entry in definite responders (21.0, SD 10.5) was significantly lower than in limited responders (24.7, SD 13.4, p < 0.001). The MDS UPDRS 3 increase over 18 months was less in definite responders at 3.0 (SD 10.4), compared to limited responders (6.4, SD 11.0, p < 0.001). The levodopa equivalent daily dose (LEDD) was not significantly different at study entry (definite responders 317 mg, SD 199, vs limited responders 305 mg, SD 191, p = 0.53). However, LEDD was significantly higher at the time of the L-dopa challenge test in definite responders (541 mg, SD 293) compared to limited responders (485 mg, SD 215, p = 0.01). Responsiveness to L-dopa was unaffected by the challenge test dose (p = 0.54). CONCLUSIONS: The main determinants of variation in the L-dopa response in early PD are age and motor severity. A limited L-dopa response is associated with faster motor progression.
Authors: W R Wayne Martin; Michael Miles; Qiaonan Zhong; Johanna Hartlein; Brad A Racette; Scott A Norris; Mwiza Ushe; Baijayanta Maiti; Susan Criswell; Albert A Davis; Paul T Kotzbauer; Nigel J Cairns; Richard J Perrin; Joel S Perlmutter Journal: Mov Disord Date: 2020-11-30 Impact factor: 10.338
Authors: Felipe Patricio; Alan Axel Morales-Andrade; Aleidy Patricio-Martínez; Ilhuicamina Daniel Limón Journal: Front Pharmacol Date: 2020-12-15 Impact factor: 5.810