Clinical and brain imaging characteristics in leucine-rich repeat kinase 2–associated PD and asymptomatic mutation carriers§

Authors

  • Kathrin Brockmann MD,

    Corresponding author
    1. Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
    2. 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, Germany
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  • Adriane Gröger PhD,

    1. Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
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  • Adriana Di Santo MD,

    1. Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
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  • Inga Liepelt PhD,

    1. Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
    2. German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
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  • Claudia Schulte PhD,

    1. Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
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  • Uwe Klose PhD,

    1. MR-Research Group, Department of Diagnostic and Interventional Neuroradiology, University of Tübingen, Tübingen, Germany
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  • Walter Maetzler MD,

    1. Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
    2. German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
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  • Ann-Kathrin Hauser,

    1. Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
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  • Ruediger Hilker MD,

    1. Department of Neurology and Brain Imaging Center, University of Frankfurt, Frankfurt, Germany
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  • Baltazar Gomez-Mancilla PhD,

    1. Novartis Institute of Biomedical Research at Novartis, Basel, Switzerland
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  • Daniela Berg MD,

    1. Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
    2. German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
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  • Thomas Gasser MD

    1. Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
    2. German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
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  • Funding 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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