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Contextualizing the pathology in the essential tremor cerebellar cortex: a patholog-omics approach
Elan D Louis1,2,3, Chloë A Kerridge4, Debotri Chatterjee4
1Department of Neurology, Yale School of Medicine, Yale University, 15 York Street, PO Box 208018, New Haven, CT, 06520-8018, USA. elan.louis@yale.edu.
Acta Neuropathologica
|July 19, 2019
Summary
Essential tremor (ET) shows mild cerebellar degeneration, aligning it with less severe neurodegenerative disorders. Distinct pathological patterns differentiate ET from other conditions like spinocerebellar ataxias (SCAs).
Area of Science:
- Neuroscience
- Neuropathology
- Cerebellar Disorders
Background:
- Essential tremor (ET) exhibits Purkinje cell (PC) morphological changes in the cerebellum.
- These changes lack context within a broader spectrum of neurodegenerative diseases.
- Understanding ET's pathology requires comparison with other cerebellar and related disorders.
Purpose of the Study:
- To compare the severity and patterns of cerebellar cortical degeneration in ET.
- To contrast ET with spinocerebellar ataxias (SCAs), multiple system atrophy (MSA), Parkinson's disease (PD), and dystonia.
- To contextualize ET's cerebellar pathology within the spectrum of neurodegenerative diseases.
Main Methods:
- Postmortem analysis of 156 brains across ET, SCAs, MSA, PD, dystonia, and control groups.
- Quantitative assessment of 37 morphological metrics related to Purkinje cells and cerebellar circuitry.
- Principal component analysis (PCA) to compare diagnostic groups based on pathological metrics.
Main Results:
- Diagnostic groups showed non-uniform cerebellar pathology.
- ET exhibited changes in 21/37 metrics, aligning it with milder cerebellar degeneration.
- Distinct pathological patterns were identified for ET, SCAs, MSA, PD, and dystonia.
Conclusions:
- Essential tremor's cerebellar degeneration is mild, placing it at the lower end of the degenerative spectrum.
- Each disorder analyzed possesses a unique signature of cerebellar degenerative changes.
- Comparative neuropathology is crucial for understanding the specific disease mechanisms in ET and related disorders.
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