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Alterations of motor cortical excitability and anatomy in Unverricht-Lundborg disease

Authors

  • Nils Danner MD, PhD,

    Corresponding author
    1. Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
    2. Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland
    • Correspondence to: Dr. Nils Danner, Kuopio University Hospital, Department of Clinical Neurophysiology, P.O. Box 1777, FI-70211 Kuopio, Finland; danner@student.uef.fi

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  • Petro Julkunen PhD,

    1. Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland
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  • Jelena Hyppönen MD, PhD,

    1. Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland
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  • Eini Niskanen PhD,

    1. Department of Clinical Radiology, Kuopio University Hospital, Kuopio, Finland
    2. Department of Applied Physics, University of Eastern Finland, Kuopio, Finland
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  • Laura Säisänen PhD,

    1. Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
    2. Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland
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  • Mervi Könönen MSc,

    1. Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland
    2. Department of Clinical Radiology, Kuopio University Hospital, Kuopio, Finland
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  • Päivi Koskenkorva MD, PhD,

    1. Department of Clinical Radiology, Kuopio University Hospital, Kuopio, Finland
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  • Ritva Vanninen MD, PhD,

    1. Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
    2. Department of Clinical Radiology, Kuopio University Hospital, Kuopio, Finland
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  • Reetta Kälviäinen MD, PhD,

    1. Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
    2. Department of Neurology, Kuopio University Hospital, Kuopio, Finland
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  • Esa Mervaala MD, PhD

    1. Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
    2. Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland
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  • Funding agencies: The study was funded by the Regional Fund of Northern-Savo of the Finnish Cultural Foundation, the Instrumentarium Science Foundation, the Epilepsy Research Foundation, the Maud Kuistila Memorial Foundation, the Orion-Farmos Research Foundation, the Maire Taponen Foundation, the Emil Aaltonen Foundation, the Academy of Finland, UCB Pharma, and the Vaajasalo Foundation.

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the Acknowledgments section online.

ABSTRACT

Unverricht-Lundborg disease is the most common form of progressive myoclonus epilepsies. In addition to generalized seizures, it is characterized by myoclonus, which usually is the most disabling feature of the disease. Classically, the myoclonus has been attributed to increased excitability of the primary motor cortex. However, inhibitory cortical phenomena have also been described along with anatomical alterations. We aimed to characterize the relationship between the excitability and anatomy of the motor cortex and their association with the severity of the clinical symptoms. Seventy genetically verified patients were compared with forty healthy controls. The symptoms were evaluated with the Unified Myoclonus Rating Scale. Navigated transcranial magnetic stimulation was applied to characterize the excitability of the primary motor cortex by determining the motor thresholds and cortical silent periods. In addition, the induced cortical electric fields were estimated using individual scalp-to-cortex distances measured from MRIs. A cortical thickness analysis was performed to elucidate possible disease-related anatomical alterations. The motor thresholds, cortical electric fields, and silent periods were significantly increased in the patients (P < 0.01). The silent periods correlated with the myoclonus scores (r = 0.48 to r = 0.49, P < 0.001). The scalp-to-cortex distance increased significantly with disease duration (r = 0.56, P < 0.001) and correlated inversely with cortical thickness. The results may reflect the refractory nature of the myoclonus and indicate a possible reactive cortical inhibitory mechanism to the underlying disease process. This is the largest clinical series on Unverricht-Lundborg disease and the first study describing parallel pathophysiological and structural alterations associated with the severity of the symptoms. © 2013 International Parkinson and Movement Disorder Society

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