Abstract Details

Title Histopathology of the Cerebellar Cortex in Essential Tremor and Other Neurodegenerative Motor Disorders: Comparative Analysis of 311 Brains

Topic Movement Disorders

Presentation(s) S32 - Movement Disorders: Dystonia and Tremor Disorders (4:42 PM-4:54 PM)

Poster/Presentation
Number 007

Background Several morphological changes, centered in/around Purkinje cells (PCs), have been identified in the cerebellum of ET patients. These changes have not been fully contextualized within a broader degenerative disease spectrum.

Objective We compared the severity and patterning of degenerative changes within the cerebellar cortex in essential tremor (ET) patients, other neurodegenerative disorders of the cerebellum (spinocerebellar ataxias, SCAs), and other disorders that may involve the cerebellum (Parkinson’s disease [PD], dystonia].

Design/Methods Using a postmortem series of 311 brains [100 ET, 47 SCA (13 SCA3; 34 SCA1, 2, 6, 7, 8, 14), 4 Friedreich’s ataxia (FA), 29 multiple system atrophy (MSA), 62 PD, 19 dystonia, 50 controls], we generated data on 37 quantitative morphologic metrics, which were grouped into 8 broad categories: (1) PC loss, (2) heterotopic PCs, (3) PC dendritic changes, (4) PC axonal changes (torpedoes), (5) PC axonal changes (other than torpedoes), (6) PC axonal changes (torpedo-associated), (7) basket cell axonal hypertrophy, (8) climbing fiber-PC synaptic changes. Analyses used z scored raw data for each metric across all diagnoses (11,507 total data items).

Results Principal component analysis revealed that diagnostic groups were not uniform with respect to pathology. Dystonia and PD each differed from controls in only 5/37 metrics, whereas ET differed in 21, FA in 3, SCA3 in 10, MSA in 21, and SCA1/2/6/7/8/14 in 27. Comparing ET with primary disorders of cerebellar degeneration (i.e., SCAs), we observed a spectrum of changes reflecting differences of degree, being generally mild in ET, FA and SCA3 and more severe in SCA1/2/6/7/8/14. Comparative analyses across morphologic categories demonstrated differences in relative expression, defining distinctive patterns of changes in these groups.

Conclusions

The degree of cerebellar degeneration in ET aligns it with the milder end in the spectrum of cerebellar degenerative disorders, and a somewhat distinctive signature of degenerative changes marks each of these disorders.

Authors/Disclosures
Elan D. Louis, MD, MS, FAAN (University of Texas Southwestern Medical Center) PRESENTER	Dr. Louis has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wolters Kluwer - Merritt's Textbook of Neurology. Dr. Louis has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Legal Firm. The institution of Dr. Louis has received research support from National Institutes of Health. Dr. Louis has received publishing royalties from a publication relating to health care.
	No disclosure on file
Morgan McCreary	No disclosure on file
Sheng-Han Kuo, MD (Columbia University)	Dr. Kuo has nothing to disclose.
	No disclosure on file
Phyllis Faust	No disclosure on file