Clinical and brain imaging characteristics in leucine-rich repeat kinase 2–associated PD and asymptomatic mutation carriers†‡§
Corresponding Author
Kathrin Brockmann MD
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Department of Neurodegeneration, Hertie-Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Str. 3, D - 72076 Tübingen, GermanySearch for more papers by this authorAdriane Gröger PhD
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
Search for more papers by this authorAdriana Di Santo MD
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
Search for more papers by this authorInga Liepelt PhD
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Search for more papers by this authorClaudia Schulte PhD
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
Search for more papers by this authorUwe Klose PhD
MR-Research Group, Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany
Search for more papers by this authorWalter Maetzler MD
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Search for more papers by this authorAnn-Kathrin Hauser
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
Search for more papers by this authorRuediger Hilker MD
Department of Neurology and Brain Imaging Center, University of Frankfurt, Frankfurt, Germany
Search for more papers by this authorBaltazar Gomez-Mancilla PhD
Novartis Institute of Biomedical Research at Novartis, Basel, Switzerland
Search for more papers by this authorDaniela Berg MD
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Search for more papers by this authorThomas Gasser MD
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Search for more papers by this authorCorresponding Author
Kathrin Brockmann MD
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Department of Neurodegeneration, Hertie-Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Str. 3, D - 72076 Tübingen, GermanySearch for more papers by this authorAdriane Gröger PhD
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
Search for more papers by this authorAdriana Di Santo MD
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
Search for more papers by this authorInga Liepelt PhD
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Search for more papers by this authorClaudia Schulte PhD
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
Search for more papers by this authorUwe Klose PhD
MR-Research Group, Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany
Search for more papers by this authorWalter Maetzler MD
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Search for more papers by this authorAnn-Kathrin Hauser
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
Search for more papers by this authorRuediger Hilker MD
Department of Neurology and Brain Imaging Center, University of Frankfurt, Frankfurt, Germany
Search for more papers by this authorBaltazar Gomez-Mancilla PhD
Novartis Institute of Biomedical Research at Novartis, Basel, Switzerland
Search for more papers by this authorDaniela Berg MD
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Search for more papers by this authorThomas Gasser MD
Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Search for more papers by this authorFunding agencies: This study was supported by Novartis Pharma AG.
Relevant conflicts of interest/financial disclosures: Nothing to report.
Full financial disclosures and author roles may be found in the online version of this article.
Abstract
The objective of this research was to evaluate a possible endophenotype in leucine-rich repeat kinase 2 (LRRK2)-associated Parkinson's disease (PD). Ten symptomatic LRRK2 patients, 24 sporadic Parkinson's disease patients as well as 10 asymptomatic LRRK2 mutation carriers and 29 matched healthy controls underwent comprehensive clinical assessments with respect to motor and non-motor symptoms. Transcranial sonography and magnetic resonance imaging (voxel-based morphometry [VBM]) were assessed to evaluate morphological imaging characteristics. LRRK2 patients had an earlier onset of motor symptoms and a more benign phenotype of motor and non-motor characteristics compared to sporadic Parkinson's disease patients. However, depression scores were higher in LRRK2 patients. No clinical differences were found regarding motor and non-motor symptoms in asymptomatic LRRK2 mutation carriers in comparison to controls. Transcranial sonography showed hyperechogenicity of the substantia nigra in both patients' cohorts as well as in asymptomatic LRRK2 mutation carriers. Voxel-based morphometry revealed increased gray matter volume of the cerebellum and precentral gyrus in LRRK2 patients and of the cuneus in asymptomatic LRRK2 mutation carriers. In contrast, we found decreased basal ganglia gray matter volume in LRRK2 patients compared to controls. Increased gray matter volume of different anatomical structures associated with motor loops in LRRK2 patients and asymptomatic LRRK2 mutation carriers compared to age-matched sporadic Parkinson's disease patients and controls might indicate compensatory mechanism in LRRK2 mutation carriers due to motor network plasticity not only in the symptomatic stage of the disease but even in the premotor phase. Substantia nigra hyperechogenicity in yet unaffected LRRK2 mutation carriers indicates morphologic alterations in an asymptomatic stage of disease. © 2011 Movement Disorder Society
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