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Cerebellar Pathology in Early Onset and Late Onset Essential Tremor

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Abstract

Early onset and late onset essential tremor (ET) cases differ in several respects. Whether they differ with respect to cerebellar pathologic changes remains to be determined. We quantified a broad range of postmortem features (Purkinje cell (PC) counts, PC axonal torpedoes and associated axonal changes, heterotopic PCs, and hairy basket ratings) in 30 ET cases with age of tremor onset <50 years, 30 ET cases with age of tremor onset ≥50 years, and 30 controls (total n = 90). We also used two alternative age of onset cut-points (<40 vs. ≥40 years, and <60 vs. ≥60 years) to define early onset vs. late onset ET. We found that ET cases with tremor onset <50 years and tremor onset ≥50 years had similar PC counts (8.78 ± 1.70 vs. 8.86 ± 1.24, p = 0.839), PC axonal torpedo counts (17.87 ± 18.27 [median =13.00] vs. 12.90 ± 10.60 [median =9.0], p = 0.486) and associated axonal pathology (all p values >0.05), heterotopic PC counts (9.90 ± 11.55 [median =6.00] vs. 5.40 ± 5.10 [median =3.50], p = 0.092), and hairy basket ratings (1.95 ± 0.62 [median =2.00] vs. 2.05 ± 0.92 [median =2.00], p = 0.314). When using the age of onset cut-points of 40 or 60 years, results were similar. Early onset and late onset ET cases share similar cerebellar postmortem features. These data do not support the notion that these age-of-onset related forms of ET represent distinct clinical-pathological entities.

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Author’s Contribution

List all authors along with their specific roles in the project and preparation of the manuscript. These may include but are not restricted to: (1) research project: A. conception, B. organization, C. execution; (2) statistical analysis: A. design, B. execution, C. review and critique; (3) manuscript: A. writing of the first draft, B. review and critique.

Sheng-Han Kuo: 1A, 1B, 1C, 2A, 2B, 3A

Jie Wang: 1B, 1C, 2A, 2B, 3B

William Tate: 1C, 3B

Ming-Kai Pan: 1C, 3B

Geoffrey Kelly: 1C, 3B

Jesus Gutierrez: 1C, 3B

Phyllis Faust: 1A, 1B, 1C, 3B

Elan Louis: 1A, 1B, 2A, 2C, 3B.

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Authors and Affiliations

  1. Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Sheng-Han Kuo, Jie Wang & Ming-Kai Pan

  2. Neurological Institute, Columbia University, New York, NY, 10032, USA

    Sheng-Han Kuo

  3. Department of Basic and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, Jiangsu Province, China

    Jie Wang

  4. Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, NY, USA

    William J. Tate, Geoffrey C. Kelly, Etty P. Cortes, Jean-Paul G. Vonsattel & Phyllis L. Faust

  5. Department of Medical Research, National Taiwan University, Taipei, Taiwan

    Ming-Kai Pan

  6. Department of Neurology, Yale School of Medicine, Yale University, New Haven, CT, USA

    Jesus Gutierrez & Elan D. Louis

  7. Taub Institute for Research on Alzheimer’s disease and the Aging Brain, Columbia University, New York, NY, USA

    Etty P. Cortes & Jean-Paul G. Vonsattel

  8. Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, USA

    Elan D. Louis

  9. Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, CT, USA

    Elan D. Louis

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  1. Sheng-Han Kuo
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Correspondence to Sheng-Han Kuo.

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Funding

Dr. Kuo has received funding from the National Institutes of Health: NINDS #K08 NS083738 (principal investigator), and the Louis V. Gerstner Jr. Scholar Award, Parkinson’s Disease Foundation, and International Essential Tremor Foundation. Dr. Wang has received funding from the Jiangsu Government Scholarship for Overseas studies supported by Jiangsu Provincial Department of Education, China and the Key Discipline Development Project of Jiangsu Province, China (Nursing, Grant No. JX10617801). Dr. Louis has received research support from the National Institutes of Health: NINDS No. R01 NS042859 (principal investigator), NINDS No. R01 NS39422 (principal investigator), NINDS No. R01 NS086736 (principal investigator), NINDS No. R01 NS073872 (principal investigator), NINDS No. R01 NS085136 (principal investigator) and NINDS No. R01 NS088257 (principal investigator). He has also received support from the Claire O’Neil Essential Tremor Research Fund (Yale University). Dr. Faust has received funding from the National Institutes of Health: NINDS No. R21 NS077094 (principal investigator) and NINDS No. R01 NS39422 (principal investigator).

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The authors declare that they have no conflicts of interest.

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Kuo, SH., Wang, J., Tate, W.J. et al. Cerebellar Pathology in Early Onset and Late Onset Essential Tremor. Cerebellum 16, 473–482 (2017). https://doi.org/10.1007/s12311-016-0826-5

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