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Contextualizing the pathology in the essential tremor cerebellar cortex: a patholog-omics approach
- Source :
- Acta Neuropathol
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- 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.
- Subjects :
- Male
0301 basic medicine
Cerebellum
Pathology
medicine.medical_specialty
Degenerative Disorder
Essential Tremor
Biology
Article
Pathology and Forensic Medicine
Cerebellar Cortex
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Degenerative disease
medicine
Cerebellar Degeneration
Humans
Spinocerebellar Ataxias
Aged
Aged, 80 and over
Dystonia
Essential tremor
Parkinson Disease
Middle Aged
Multiple System Atrophy
medicine.disease
Axons
030104 developmental biology
medicine.anatomical_structure
nervous system
Dystonic Disorders
Cerebellar cortex
Spinocerebellar ataxia
Female
sense organs
Neurology (clinical)
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 14320533 and 00016322
- Volume :
- 138
- Database :
- OpenAIRE
- Journal :
- Acta Neuropathologica
- Accession number :
- edsair.doi.dedup.....93e89d6e355a8ecb85aab50bedd93fec