Brain Advance Access published online on November 19, 2007
Brain, doi:10.1093/brain/awm266
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Neuropathological changes in essential tremor: 33 cases compared with 21 controls
1GH Sergievsky Center, 2Department of Neurology, 3Taub Institute for Research on Alzheimer's Disease and the Aging Brain, 4Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, 5Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA, 6Royal University Hospital, Saskatoon, Saskatchewan, Canada, 7Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA, 8Veterans Affairs Pacific Islands Health Care System, 9Departments of Medicine and Geriatrics, University of Hawaii John A. Burns School of Medicine, 10Pacific Health Research Institute and 11Kuakini Medical Center/Honolulu-Asia Aging Study, Honolulu, HI, USA
Correspondence to:
Dr Elan Louis, Unit 198, Neurological Institute, 710 West 168th Street, New York, NY 10032, USA. E-mail: EDL2{at}columbia.edu
Despite its being one of the most commonly observed neurological disorders, neuropathological studies of essential tremor (ET) are rare. There have been surprisingly few autopsy studies and even fewer case-control comparisons. The primary objective was to describe and quantify the pathological changes in 33 ET and 21 control brains. A secondary objective was to correlate clinical and pathological features. We examined autopsy tissue from the Essential Tremor Centralized Brain Repository. Eight (24.2%) of the 33 ET brains had Lewy bodies in the brainstem, mainly in the locus ceruleus. However, the majority of ET brains (25/33, 75.8%) had no Lewy bodies, but had pathological changes in the cerebellum. The mean number of Purkinje cells per 100x field was reduced in ET cases without Lewy bodies (6.6 ± 2.4 versus 9.6 ± 3.4, P < 0.01), and there were 
7x more Purkinje cell torpedoes per section (12.6 ± 7.9 versus 1.7 ± 1.4, P < 0.001) compared to controls. ET cases without Lewy bodies also had degeneration of the dentate nucleus (two cases). Other findings in ET cases were Purkinje cell heterotopias and dendrite swellings. Lewy body ET cases were older than ET cases without Lewy bodies. Several trends were observed in ET cases without Lewy bodies, including a younger age of onset of tremor and higher proportions with gait difficulty and family history of ET. The pathological changes of ET seem to be heterogeneous and degenerative. The majority have cerebellar changes without Lewy bodies; a smaller proportion has brainstem Lewy bodies. The clinical differences between cases with versus without Lewy bodies require additional study.
Key Words: essential tremor; cerebellum; Purkinje cell; Lewy body; neurodegeneration; locus ceruleus
Abbreviations: ET, essential tremor; GFAP, glial fibrillary acidic protein
Received May 25, 2007. Revised October 9, 2007. Accepted October 11, 2007.