| Autor: |
Louis ED; Department of Neurology, Yale School of Medicine, Yale University, 15 York Street, PO Box 208018, New Haven, CT, 06520-8018, USA. elan.louis@yale.edu.; Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, USA. elan.louis@yale.edu.; Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, CT, USA. elan.louis@yale.edu., Kerridge CA; Department of Pathology and Cell Biology, Columbia University Irving Medical Center and the New York Presbyterian Hospital, 622 West 168th Street, PH Stem 1564, New York, NY, 10032, USA., Chatterjee D; Department of Pathology and Cell Biology, Columbia University Irving Medical Center and the New York Presbyterian Hospital, 622 West 168th Street, PH Stem 1564, New York, NY, 10032, USA., Martuscello RT; Department of Pathology and Cell Biology, Columbia University Irving Medical Center and the New York Presbyterian Hospital, 622 West 168th Street, PH Stem 1564, New York, NY, 10032, USA., Diaz DT; Department of Neurology, Yale School of Medicine, Yale University, 15 York Street, PO Box 208018, New Haven, CT, 06520-8018, USA., Koeppen AH; Research, Neurology, and Pathology Services, Veterans Affairs Medical Center and Departments of Neurology and Pathology, Albany Medical College, Albany, NY, USA., Kuo SH; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA., Vonsattel JG; Department of Pathology and Cell Biology, Columbia University Irving Medical Center and the New York Presbyterian Hospital, 622 West 168th Street, PH Stem 1564, New York, NY, 10032, USA.; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA., Sims PA; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, 10032, USA.; Sulzberger Columbia Genome Center, Columbia University Irving Medical Center, New York, NY, USA.; Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, NY, USA., Faust PL; Department of Pathology and Cell Biology, Columbia University Irving Medical Center and the New York Presbyterian Hospital, 622 West 168th Street, PH Stem 1564, New York, NY, 10032, USA. plf3@cumc.columbia.edu. |
| Abstrakt: |
Several morphological changes, centered in/around Purkinje cells (PCs), have been identified in the cerebellum of essential tremor (ET) patients. These changes have not been contextualized within a broader degenerative disease spectrum, limiting their interpretability. To address this, we compared the severity and patterning of degenerative changes within the cerebellar cortex in patients with ET, other neurodegenerative disorders of the cerebellum (spinocerebellar ataxias (SCAs), multiple system atrophy (MSA)], and other disorders that may involve the cerebellum [Parkinson's disease (PD), dystonia]. Using a postmortem series of 156 brains [50 ET, 23 SCA (6 SCA3; 17 SCA 1, 2 or 6), 15 MSA, 29 PD, 14 dystonia, 25 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. Our analyses used z scored raw data for each metric across all diagnoses (5772 total data items). Principal component analysis revealed that diagnostic groups were not uniform with respect to cerebellar pathology. Dystonia and PD each differed from controls in only 2/37 metrics, whereas ET differed in 21, SCA3 in 8, MSA in 19, and SCA1/2/6 in 26 metrics. 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 and SCA3 and more severe in SCA1/2/6. Comparative analyses across morphologic categories demonstrated differences in relative expression, defining distinctive patterns of changes in these groups. Thus, the degree of cerebellar degeneration in ET aligns it with a milder end in the spectrum of cerebellar degenerative disorders, and a somewhat distinctive signature of degenerative changes marks each of these disorders. |
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