The inferior olivary nucleus: A postmortem study of essential tremor cases versus controls

Authors

  • Elan D. Louis MD, MSc,

    Corresponding author
    1. G. H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    2. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    3. Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    4. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA
    • Correspondence to: Dr. E. D. Louis, Unit 198, Neurological Institute, 710 West 168th Street, New York, NY, 10032; edl2@columbia.edu

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  • Rachel Babij BS,

    1. G. H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York, USA
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  • Etty Cortés MD,

    1. Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, New York, USA
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  • Jean-Paul G. Vonsattel MD,

    1. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    2. Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, New York, USA
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  • Phyllis L. Faust MD, PhD

    1. Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, New York, USA
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  • Funding agencies: This work was supported by grant R01 NS042859 from the National Institutes of Health (Bethesda, MD) and by the Claire O'Neil Essential Tremor Research Fund (Columbia University, New York, NY).

  • 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 pathogenesis of essential tremor is poorly understood. Historically, it has been hypothesized that the inferior olivary nucleus plays an important role in the generation of tremor in essential tremor, yet a detailed, controlled, anatomic-pathological study of that brain region has yet to be conducted. A detailed postmortem study was undertaken of the microscopic changes in the inferior olivary nucleus of 14 essential tremor cases versus 15 age-matched controls at the Essential Tremor Centralized Brain Repository. A series of metrics was used to quantify microscopic neuronal and glial changes in the inferior olivary nucleus and its input and output tracts. Olivary linear neuronal density also was assessed. Cases and controls did not differ from one another with respect to any of the assessed metrics (P values ranged from 0.23 to 1.0). Olivary linear neuronal density also was similar in cases and controls (P = 0.62). Paddle-shaped neurons, a morphologic shape change in olivary neurons, which, to our knowledge, have not been previously recognized, occurred to an equal degree in essential tremor cases and controls (P = 0.89) and were correlated with several markers of neuronal loss and gliosis. A systematic postmortem study of the microscopic changes in the inferior olivary nucleus did not detect any differences between cases and controls. These data, along with positron emission tomography data, which have failed to identify any metabolic abnormality of the olive, indicate that, if the olive is involved in essential tremor, then there is no clearly identifiable structural or metabolic correlate. © 2013 Movement Disorder Society

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