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Changes in the Purkinje cells (PCs) and climbing fibers (CFs) have been postulated to be involved in essential tremor (ET) disease pathogenesis.1 PCs receive 2 excitatory inputs: CFs and parallel fibers (PFs). CFs form synapses predominantly on the thick, proximal PC dendrites, whereas PFs form synapses on the thin, distal PC dendritic branchlets. CF-PC and PF-PC innervation territories on PC dendritic arbors are tightly regulated for proper PC function. We recently reported more CF-PC synapses on the thin, distal PC dendritic branchlets in ET cases than controls,2 and this pathologic feature was associated with tremor severity in a small sample of 8 ET cases. We now expand the ET case sample nearly fivefold (37 cases) and assess the association between abnormal CF-PC connections and a wider range of clinical features. The overarching goal was to begin to mark out clinical characteristics that track with pathologic features in ET.
Acknowledgments
Acknowledgment: The authors thank Dr. Elan Louis for editing the manuscript.
Footnotes
Author contributions: Ravi Louis: acquisition of data, analysis and interpretation, critical revision of the manuscript for important intellectual content. Chi-Ying Lin: study concept and design, analysis and interpretation, critical revision of the manuscript for important intellectual content. Phyllis Faust: analysis and interpretation, critical revision of the manuscript for important intellectual content. Arnulf Koeppen: critical revision of the manuscript for important intellectual content. Sheng-Han Kuo: study concept and design, analysis and interpretation, critical revision of the manuscript for important intellectual content.
Study funding: Dr. Kuo has received funding from the National Institute of Neurological Disorders and Stroke #K08 NS08738 (principal investigator), Louis V. Gerstner Jr. Scholar Award, Parkinson's Disease Foundation, American Brain Foundation Research Fellowship, Parkinson's Disease Foundation, American Parkinson's Disease Association, International Essential Tremor Foundation, NIEHS pilot award #ES009089.
Disclosure: The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.
- Received October 7, 2014.
- Accepted in final form January 26, 2015.
- © 2015 American Academy of Neurology
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