Histopathology of the cerebellar cortex in essential tremor and other neurodegenerative motor disorders: comparative analysis of 320 brains.

Autor: Louis ED; Department of Neurology, University of Texas Southwestern, 5323 Harry Hines Blvd, Dallas, TX, 75390-8813, USA. elan.louis@UTSouthwestern.edu., Martuscello RT; Department of Pathology and Cell Biology, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY, USA., Gionco JT; Department of Pathology and Cell Biology, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY, USA., Hartstone WG; Department of Pathology and Cell Biology, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY, USA., Musacchio JB; Department of Pathology and Cell Biology, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY, USA., Portenti M; Department of Pathology and Cell Biology, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY, USA., McCreary M; Department of Neurology, University of Texas Southwestern, 5323 Harry Hines Blvd, Dallas, TX, 75390-8813, USA., Kuo SH; Department of Neurology, Vagelos 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, New York, NY, USA.; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA., Faust PL; Department of Pathology and Cell Biology, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY, USA.
Jazyk: angličtina
Zdroj: Acta neuropathologica [Acta Neuropathol] 2023 Mar; Vol. 145 (3), pp. 265-283. Date of Electronic Publication: 2023 Jan 06.
DOI: 10.1007/s00401-022-02535-z
Abstrakt: In recent years, numerous morphologic changes have been identified in the essential tremor (ET) cerebellar cortex, distinguishing ET from control brains. These findings have not been fully contextualized within a broader degenerative disease spectrum, thus limiting their interpretability. Building off our prior study and now doubling the sample size, we conducted comparative analyses in a postmortem series of 320 brains on the severity and patterning of cerebellar cortex degenerative changes in ET (n = 100), other neurodegenerative disorders of the cerebellum [spinocerebellar ataxias (SCAs, n = 47, including 13 SCA3 and 34 SCA1, 2, 6, 7, 8, 14); Friedreich's ataxia (FA, n = 13); multiple system atrophy (MSA), n = 29], and other disorders that may involve the cerebellum [Parkinson's disease (PD), n = 62; dystonia, n = 19] versus controls (n = 50). We generated data on 37 quantitative morphologic metrics, grouped into 8 broad categories: Purkinje cell (PC) loss, heterotopic PCs, PC dendritic changes, PC axonal changes (torpedoes), PC axonal changes (other than torpedoes), PC axonal changes (torpedo-associated), basket cell axonal hypertrophy, and climbing fiber-PC synaptic changes. Principal component analysis of z scored raw data across all diagnoses (11,651 data items) revealed that diagnostic groups were not uniform with respect to pathology. Dystonia and PD each differed from controls in only 4/37 and 5/37 metrics, respectively, whereas ET differed in 21, FA in 10, SCA3 in 10, MSA in 21, and SCA1/2/6/7/8/14 in 27. Pathological changes were generally on the milder end of the degenerative spectrum in ET, FA and SCA3, and on the more severe end of that spectrum 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. In summary, we present a robust and reproducible method that identifies somewhat distinctive signatures of degenerative changes in the cerebellar cortex that mark each of these disorders.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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