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In Vivo Dentate Nucleus Gamma-aminobutyric Acid Concentration in Essential Tremor vs. Controls

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Abstract

Despite its high prevalence, essential tremor (ET) is among the most poorly understood neurological diseases. The presence and extent of Purkinje cell (PC) loss in ET is the subject of controversy. PCs are a major storehouse of central nervous system gamma-aminobutyric acid (GABA), releasing GABA at the level of the dentate nucleus. It is therefore conceivable that cerebellar dentate nucleus GABA concentration could be an in vivo marker of PC number. We used in vivo 1H magnetic resonance spectroscopy (MRS) to quantify GABA concentrations in two cerebellar volumes of interest, left and right, which included the dentate nucleus, comparing 45 ET cases to 35 age-matched controls. 1H MRS was performed using a 3.0-T Siemens Tim Trio scanner. The MEGA-PRESS J-editing sequence was used for GABA detection in two cerebellar volumes of interest (left and right) that included the dentate nucleus. The two groups did not differ with respect to our primary outcome of GABA concentration (given in institutional units). For the right dentate nucleus, [GABA] in ET cases = 2.01 ± 0.45 and [GABA] in controls = 1.86 ± 0.53, p = 0.17. For the left dentate nucleus, [GABA] in ET cases = 1.68 ± 0.49 and [GABA] controls = 1.80 ± 0.53, p = 0.33. The controls had similar dentate nucleus [GABA] in the right vs. left dentate nucleus (p = 0.52); however, in ET cases, the value on the right was considerably higher than that on the left (p = 0.001). We did not detect a reduction in dentate nucleus GABA concentration in ET cases vs. controls. One interpretation of the finding is that it does not support the existence of PC loss in ET; however, an alternative interpretation is the observed pattern could be due to the effects of terminal sprouting in ET (i.e., collateral sprouting from surviving PCs making up for the loss of GABA-ergic terminals from PC degeneration). Further research is needed.

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Acknowledgements

This work was supported by NINDS R01 NS085136 from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Neurology, Yale School of Medicine, Yale University, LCI 710, 15 York Street, PO Box 208018, New Haven, CT, 06520-8018, USA

    Elan D. Louis & Nora Hernandez

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

    Elan D. Louis

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

    Elan D. Louis

  4. Department of Radiology, Weill Cornell Medical College, New York, NY, USA

    Jonathan P. Dyke

  5. School of Health Sciences, Purdue University, West Lafayette, IN, USA

    Ruoyun E. Ma & Ulrike Dydak

  6. Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA

    Ruoyun E. Ma & Ulrike Dydak

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  1. Elan D. Louis
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Correspondence to Elan D. Louis.

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The study protocol was approved by the Human Subjects Institutional Review Board at Yale University, Purdue University, and Weill Cornell Medical College. Written informed consent was obtained from each subject upon enrollment in the study.

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The authors declare that they have no conflicts of interest.

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Louis, E.D., Hernandez, N., Dyke, J.P. et al. In Vivo Dentate Nucleus Gamma-aminobutyric Acid Concentration in Essential Tremor vs. Controls. Cerebellum 17, 165–172 (2018). https://doi.org/10.1007/s12311-017-0891-4

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