The Cerebellum

, Volume 17, Issue 2, pp 104–110 | Cite as

Heterotopic Purkinje Cells: a Comparative Postmortem Study of Essential Tremor and Spinocerebellar Ataxias 1, 2, 3, and 6

  • Elan D. Louis
  • Sheng-Han Kuo
  • William J. Tate
  • Geoffrey C. Kelly
  • Jesus Gutierrez
  • Etty P. Cortes
  • Jean-Paul G. Vonsattel
  • Phyllis L. Faust
Original Paper


Essential tremor (ET) is among the most common neurological diseases. Postmortem studies have noted a series of pathological changes in the ET cerebellum. Heterotopic Purkinje cells (PCs) are those whose cell body is mis-localized in the molecular layer. In neurodegenerative settings, these are viewed as a marker of the progression of neuronal degeneration. We (1) quantify heterotopias in ET cases vs. controls, (2) compare ET cases to other cerebellar degenerative conditions (spinocerebellar ataxias (SCAs) 1, 2, 3, and 6), (3) compare these SCAs to one another, and (4) assess heterotopia within the context of associated PC loss in each disease. Heterotopic PCs were quantified using a standard LH&E-stained section of the neocerebellum. Counts were normalized to PC layer length (n-heterotopia count). It is also valuable to consider PC counts when assessing heterotopia, as loss of PCs extends both to normally located as well as heterotopic PCs. Therefore, we divided n-heterotopias by PC counts. There were 96 brains (43 ET, 31 SCA [12 SCA1, 7 SCA2, 7 SCA3, 5 SCA6], and 22 controls). The median number of n-heterotopias in ET cases was two times higher than that of the controls (2.6 vs. 1.2, p < 0.05). The median number of n-heterotopias in the various SCAs formed a spectrum, with counts being highest in SCA3 and SCA1. In analyses that factored in PC counts, ET had a median n-heterotopia/Purkinje cell count that was three times higher than the controls (0.35 vs. 0.13, p < 0.01), and SCA1 and SCA2 had counts that were 5.5 and 11 times higher than the controls (respective p < 0.001). The median n-heterotopia/PC count in ET was between that of the controls and the SCAs. Similarly, the median PC count in ET was between that of the controls and the SCAs; the one exception was SCA3, in which the PC population is well known to be preserved. Heterotopia is a disease-associated feature of ET. In comparison, several of the SCAs evidenced even more marked heterotopia, although a spectrum existed across the SCAs. The median n-heterotopia/PC count and median PC in ET was between that of the controls and the SCAs; hence, in this regard, ET could represent an intermediate state or a less advanced state of spinocerebellar atrophy.


Essential tremor Spinocerebellar ataxia Cerebellum Neurodegenerative Purkinje cell Pathology Heterotopia 



Nine control brains were from the Harvard Brain Tissue Resource Center (McLean Hospital, Belmont, MA). Dr. Arnulf H. Koeppen, Veterans Affairs Medical Center, Albany, New York, USA, provided human SCA1, SCA2, and SCA6 tissues. Human SCA2 and SCA3 tissues were also obtained from the NIH NeuroBioBank at the University of Maryland, Baltimore, MD. An SCA3 human tissue specimen was also obtained from Dr. José Luiz Pedroso, Ataxia Unit Federal University of Sao Paulo, Sao Paulo, Brazil.

Dr. Louis has received research support from the National Institutes of Health: NINDS #R01 NS094607 (principal investigator), NINDS #R01 NS39422 (principal investigator), NINDS #R01 NS046436 (principal investigator), NINDS #R01 NS073872 (principal investigator), NINDS #R01 NS085136 (principal investigator), and NINDS #R01 NS088257 (principal investigator). He has also received support from the Claire O’Neil Essential Tremor Research Fund (Yale University). 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. Vonsattel has received funding from the National Institutes of Health: NINDS #R01 NS088257 (coinvestigator) and NINDS #R01 NS046436 (coinvestigator). Dr. Faust has received funding from the National Institutes of Health: NINDS #R01 NS088257 (principal investigator) and NINDS #R01 NS085136 (principal investigator).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Elan D. Louis
    • 1
    • 2
    • 3
  • Sheng-Han Kuo
    • 4
  • William J. Tate
    • 5
  • Geoffrey C. Kelly
    • 5
  • Jesus Gutierrez
    • 1
  • Etty P. Cortes
    • 5
    • 6
  • Jean-Paul G. Vonsattel
    • 5
    • 6
  • Phyllis L. Faust
    • 5
  1. 1.Department of Neurology, Yale School of MedicineYale UniversityNew HavenUSA
  2. 2.Department of Chronic Disease Epidemiology, Yale School of Public HealthYale UniversityNew HavenUSA
  3. 3.Center for Neuroepidemiology and Clinical Neurological Research, Yale School of MedicineYale UniversityNew HavenUSA
  4. 4.Department of Neurology, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA
  5. 5.Department of Pathology and Cell BiologyColumbia University Medical Center and the New York Presbyterian HospitalNew YorkUSA
  6. 6.Taub Institute for Research on Alzheimer’s Disease and the Aging BrainColumbia UniversityNew YorkUSA

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