The Essential Tremor Centralized Brain Repository (ETCBR) was established in 2003 to gain a better understanding of the underlying neuropathological findings in patients with essential tremor (ET) and is now the largest repository of prospectively collected ET brains (n = 231). Hence, we are uniquely poised to address several questions, including:
- What proportion of ET cases exhibit Lewy pathology (LP)?
- What is the nature of that pathology and how does it relate to other comorbidities?
- What are the clinical correlates of that pathology?
In This Study
Each brain had a complete neuropathological assessment, including alpha-synuclein immunostaining.
We created a 10-category classification scheme to fully encapsulate the patterns of LP observed.
Four metrics of cerebellar pathology were also quantified:
- Purkinje Cell
- Torpedo (LH &E)
- Torpedo (Bielschowsky)
- Basket Rating
Results
There were 231 ET cases with a mean age at death of 89.0 ± 6.4 years. Fifty-eight (25.1%) had LP and 46 (19.9%) had early to late stages of Parkinson disease (PD). LP was very heterogeneous.
Of 58 cases with LP, 14 (24.1%) clinically developed possible PD or PD after a latency of 5 or more years. There was a similar degree of cerebellar pathology in ET cases both with and without LP.
Conclusions
1 in 4 ET cases had LP -- a proportion that seems higher than expected based on studies among control populations. Heterogeneous LP likely reflects clinical associations between ET and PD, and ET with Alzheimer disease-type neuropathology. There was evidence of cerebellar degeneration in ET cases both with and without LP, rather than just in those without LP. These data further our understanding of ET and its relatedness to other degenerative diseases.
This study was not without limitations. Patients who sign up for a brain donation are not typical ET cases. They tend to have more severe ET. Nonetheless, this is the largest prospectively collected cohort of ET brains reported to date and the most detailed clinical-pathological study of LP in this disease.
It would be of value to compare the 25.1% we observed among ET cases to other literature on the percentage of normal elderly individuals who have LP on postmortem examination.
Letter to the Editor
Read Dr. Louis & Faust’s letter to the editor “Prevalence of Lewy pathology in essential tremor is twice as high as expected: A plausible explanation for the enhanced risk for Parkinson disease seen in essential tremor cases” as a response to paper and letter from Shill et al.