Robert S Eisinger1, Christopher W Hess2, Daniel Martinez-Ramirez3, Leonardo Almeida4, Kelly D Foote5, Michael S Okun6, Aysegul Gunduz7. 1. Department of Neuroscience, Center for Movement Disorders and Neurorestoration, 3450 Hull Road, University of Florida, Gainesville, FL 32607, United States. Electronic address: eisinger@ufl.edu. 2. Department of Neurology, Center for Movement Disorders and Neurorestoration, 3450 Hull Road, University of Florida, Gainesville, FL 32607, United States. Electronic address: christopher.hess@neurology.ufl.edu. 3. Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, United States. Electronic address: daniel.martinez-ramirez@neurology.ufl.edu. 4. Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, United States. Electronic address: leonardo.britodalmeida@neurology.ufl.edu. 5. Department of Neurosurgery, Center for Movement Disorders and Neurorestoration, McKnight Brain Institute, 3rd Floor, University of Florida, Gainesville, FL 32611, United States. Electronic address: foote@neurosurgery.ufl.edu. 6. Department of Neurology, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, United States. Electronic address: okun@neurology.ufl.edu. 7. J. Crayton Pruitt Family Department of Biomedical Engineering, Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL, United States. Electronic address: agunduz@bme.ufl.edu.
Abstract
INTRODUCTION: Distinct motor subtypes of Parkinson's disease (PD) have been described through both clinical observation and through data-driven approaches. However, the extent to which motor subtypes change during disease progression remains unknown. Our objective was to determine motor subtypes of PD using an unsupervised clustering methodology and evaluate subtype changes with disease duration. METHODS: The Parkinson's Progression Markers Initiative database of 423 newly diagnosed PD patients was utilized to retrospectively identify unique motor subtypes through a data-driven, hierarchical correlational clustering approach. For each patient, we assigned a subtype to each motor assessment at each follow-up visit (time points) and by using published criteria. We examined changes in PD subtype with disease duration using both qualitative and quantitative methods. RESULTS: Five distinct motor subtypes were identified based on the motor assessment items and these included: Tremor Dominant (TD), Axial Dominant, Appendicular Dominant, Rigidity Dominant, and Postural and Instability Gait Disorder Dominant. About half of the patients had consistent subtypes at all time points. Most patients met criteria for TD subtype soon after diagnosis. For patients with inconsistent subtypes, there was an overall trend to shift away from a TD phenotype with disease duration, as shown by chi-squared test, p < 0.001, and linear regression analysis, p < 0.05. CONCLUSION: These results strongly suggest that classification of motor subtypes in PD can shift with increasing disease duration. Shifting subtypes is a factor that should be accounted for in clinical practice or in clinical trials.
INTRODUCTION: Distinct motor subtypes of Parkinson's disease (PD) have been described through both clinical observation and through data-driven approaches. However, the extent to which motor subtypes change during disease progression remains unknown. Our objective was to determine motor subtypes of PD using an unsupervised clustering methodology and evaluate subtype changes with disease duration. METHODS: The Parkinson's Progression Markers Initiative database of 423 newly diagnosed PDpatients was utilized to retrospectively identify unique motor subtypes through a data-driven, hierarchical correlational clustering approach. For each patient, we assigned a subtype to each motor assessment at each follow-up visit (time points) and by using published criteria. We examined changes in PD subtype with disease duration using both qualitative and quantitative methods. RESULTS: Five distinct motor subtypes were identified based on the motor assessment items and these included: Tremor Dominant (TD), Axial Dominant, Appendicular Dominant, Rigidity Dominant, and Postural and Instability Gait Disorder Dominant. About half of the patients had consistent subtypes at all time points. Most patients met criteria for TD subtype soon after diagnosis. For patients with inconsistent subtypes, there was an overall trend to shift away from a TD phenotype with disease duration, as shown by chi-squared test, p < 0.001, and linear regression analysis, p < 0.05. CONCLUSION: These results strongly suggest that classification of motor subtypes in PD can shift with increasing disease duration. Shifting subtypes is a factor that should be accounted for in clinical practice or in clinical trials.
Authors: Stephanie M van Rooden; Willem J Heiser; Joost N Kok; Dagmar Verbaan; Jacobus J van Hilten; Johan Marinus Journal: Mov Disord Date: 2010-06-15 Impact factor: 10.338
Authors: Maya Katz; Marta San Luciano; Kimberly Carlson; Ping Luo; William J Marks; Paul S Larson; Philip A Starr; Kenneth A Follett; Frances M Weaver; Matthew B Stern; Domenic J Reda; Jill L Ostrem Journal: Ann Neurol Date: 2015-04 Impact factor: 10.422
Authors: Glenn T Stebbins; Christopher G Goetz; David J Burn; Joseph Jankovic; Tien K Khoo; Barbara C Tilley Journal: Mov Disord Date: 2013-02-13 Impact factor: 10.338
Authors: Tanya Simuni; Jeffrey D Long; Chelsea Caspell-Garcia; Christopher S Coffey; Shirley Lasch; Caroline M Tanner; Danna Jennings; Karl D Kieburtz; Kenneth Marek Journal: Ann Clin Transl Neurol Date: 2016-05-17 Impact factor: 4.511
Authors: Robert S Eisinger; Daniel Martinez-Ramirez; Adolfo Ramirez-Zamora; Christopher W Hess; Leonardo Almeida; Michael S Okun; Aysegul Gunduz Journal: Parkinsonism Relat Disord Date: 2019-05-19 Impact factor: 4.891
Authors: Isabel Alfradique-Dunham; Rami Al-Ouran; Rainer von Coelln; Cornelis Blauwendraat; Emily Hill; Lan Luo; Amanda Stillwell; Emily Young; Anita Kaw; Manuela Tan; Calwing Liao; Dena Hernandez; Lasse Pihlstrom; Donald Grosset; Lisa M Shulman; Zhandong Liu; Guy A Rouleau; Mike Nalls; Andrew B Singleton; Huw Morris; Joseph Jankovic; Joshua M Shulman Journal: Neurol Genet Date: 2021-01-28