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The prodromal phase of leucine-rich repeat kinase 2-associated Parkinson disease: Clinical and imaging Studies.
Mov Disord. 2017 05; 32(5):726-738.MD

Abstract

BACKGROUND

Asymptomatic, nonmanifesting carriers of leucine-rich repeat kinase 2 mutations are at increased risk of developing PD. Clinical and neuroimaging features may be associated with gene carriage and/or may demarcate individuals at greater risk for phenoconversion to PD.

OBJECTIVES

To investigate clinical and dopamine transporter single-photon emission computed tomography imaging characteristics of leucine-rich repeat kinase 2 asymptomatic carriers.

METHODS

A total of 342 carriers' and 259 noncarriers' relatives of G2019S leucine-rich repeat kinase 2/PD patients and 39 carriers' and 31 noncarriers' relatives of R1441G leucine-rich repeat kinase 2/PD patients were evaluated. Motor and nonmotor symptoms were assessed using specific scales and questionnaires. Neuroimaging quantitative data were obtained in 81 carriers and compared with 41 noncarriers.

RESULTS

G2019S carriers scored higher in motor scores and had lower radioligand uptake compared to noncarriers, but no differences in nonmotor symptoms scores were observed. R1441G carriers scored higher in motor scores, had lower radioligand uptake, and had higher scores in depression, dysautonomia, and Rapid Eye Movements Sleep Behavior Disorder Screening Questionnaire scores, but had better cognition scores than noncarriers. Among G2019S carriers, a group with "mild motor signs" was identified, and was significantly older, with worse olfaction and lower radioligand uptake.

CONCLUSIONS

G2019S and R1441G carriers differ from their noncarriers' relatives in higher motor scores and slightly lower radioligand uptake. Nonmotor symptoms were mild, and different nonmotor profiles were observed in G2019S carriers compared to R1441G carriers. A group of G2019S carriers with known prodromal features was identified. Longitudinal studies are required to determine whether such individuals are at short-term risk of developing overt parkinsonism. © 2017 International Parkinson and Movement Disorder Society.

Authors+Show Affiliations

Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain. Neurology Unit, Hospital General de Granollers, Universitat Internacional de Catalunya, Granollers, Spain.Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA.Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA.Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.Departments of Neurology and Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China.Parkinson's Disease Research, Education and Clinical Center, Michael J. Crescenz VA Medical Center and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.Laboratory of Neurodegenerative Disorders, Department of Neurology, Hospital Clínic of Barcelona, Institutd'InvestigacionsBiomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, and the Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Madrid, Spain.Institute for Neurodegenerative Disorders and Molecular NeuroImaging, New Haven, Connecticut, USA.Department of Nuclear Medicine, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.Toronto Western Hospital Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, University of Toronto, Toronto, Ontario, Canada.Department of Neurology, Movement Disorders Unit. Hospital Universitario Donostia. Biodonostia Research Institute, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), San Sebastián, Guipúzcoa, Spain.Department of Neurology, Mount Sinai Beth Israel Medical Center and Icahn School of Medicine at Mount Sinai, New York, New York, USA.Department of Neurology, Norwegian University of Science and Technology, Trondheim, Norway.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28370517

Citation

Pont-Sunyer, Claustre, et al. "The Prodromal Phase of Leucine-rich Repeat Kinase 2-associated Parkinson Disease: Clinical and Imaging Studies." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 32, no. 5, 2017, pp. 726-738.
Pont-Sunyer C, Tolosa E, Caspell-Garcia C, et al. The prodromal phase of leucine-rich repeat kinase 2-associated Parkinson disease: Clinical and imaging Studies. Mov Disord. 2017;32(5):726-738.
Pont-Sunyer, C., Tolosa, E., Caspell-Garcia, C., Coffey, C., Alcalay, R. N., Chan, P., Duda, J. E., Facheris, M., Fernández-Santiago, R., Marek, K., Lomeña, F., Marras, C., Mondragon, E., Saunders-Pullman, R., & Waro, B. (2017). The prodromal phase of leucine-rich repeat kinase 2-associated Parkinson disease: Clinical and imaging Studies. Movement Disorders : Official Journal of the Movement Disorder Society, 32(5), 726-738. https://doi.org/10.1002/mds.26964
Pont-Sunyer C, et al. The Prodromal Phase of Leucine-rich Repeat Kinase 2-associated Parkinson Disease: Clinical and Imaging Studies. Mov Disord. 2017;32(5):726-738. PubMed PMID: 28370517.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The prodromal phase of leucine-rich repeat kinase 2-associated Parkinson disease: Clinical and imaging Studies. AU - Pont-Sunyer,Claustre, AU - Tolosa,Eduardo, AU - Caspell-Garcia,Chelsea, AU - Coffey,Christopher, AU - Alcalay,Roy N, AU - Chan,Piu, AU - Duda,John E, AU - Facheris,Maurizio, AU - Fernández-Santiago,Rubén, AU - Marek,Kenneth, AU - Lomeña,Francisco, AU - Marras,Connie, AU - Mondragon,Elisabet, AU - Saunders-Pullman,Rachel, AU - Waro,Bjorg, AU - ,, Y1 - 2017/03/28/ PY - 2016/06/17/received PY - 2016/12/21/revised PY - 2016/12/23/accepted PY - 2017/4/4/pubmed PY - 2018/2/7/medline PY - 2017/4/4/entrez KW - LRRK2 mutations KW - Parkinson's disease KW - nonmotor symptoms KW - prodromal phase SP - 726 EP - 738 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov. Disord. VL - 32 IS - 5 N2 - BACKGROUND: Asymptomatic, nonmanifesting carriers of leucine-rich repeat kinase 2 mutations are at increased risk of developing PD. Clinical and neuroimaging features may be associated with gene carriage and/or may demarcate individuals at greater risk for phenoconversion to PD. OBJECTIVES: To investigate clinical and dopamine transporter single-photon emission computed tomography imaging characteristics of leucine-rich repeat kinase 2 asymptomatic carriers. METHODS: A total of 342 carriers' and 259 noncarriers' relatives of G2019S leucine-rich repeat kinase 2/PD patients and 39 carriers' and 31 noncarriers' relatives of R1441G leucine-rich repeat kinase 2/PD patients were evaluated. Motor and nonmotor symptoms were assessed using specific scales and questionnaires. Neuroimaging quantitative data were obtained in 81 carriers and compared with 41 noncarriers. RESULTS: G2019S carriers scored higher in motor scores and had lower radioligand uptake compared to noncarriers, but no differences in nonmotor symptoms scores were observed. R1441G carriers scored higher in motor scores, had lower radioligand uptake, and had higher scores in depression, dysautonomia, and Rapid Eye Movements Sleep Behavior Disorder Screening Questionnaire scores, but had better cognition scores than noncarriers. Among G2019S carriers, a group with "mild motor signs" was identified, and was significantly older, with worse olfaction and lower radioligand uptake. CONCLUSIONS: G2019S and R1441G carriers differ from their noncarriers' relatives in higher motor scores and slightly lower radioligand uptake. Nonmotor symptoms were mild, and different nonmotor profiles were observed in G2019S carriers compared to R1441G carriers. A group of G2019S carriers with known prodromal features was identified. Longitudinal studies are required to determine whether such individuals are at short-term risk of developing overt parkinsonism. © 2017 International Parkinson and Movement Disorder Society. SN - 1531-8257 UR - https://www.unboundmedicine.com/medline/citation/28370517/The_prodromal_phase_of_leucine_rich_repeat_kinase_2_associated_Parkinson_disease:_Clinical_and_imaging_Studies_ L2 - https://doi.org/10.1002/mds.26964 DB - PRIME DP - Unbound Medicine ER -