A pilot study of essential tremor: cerebellar GABA+/Glx ratio is correlated with tremor severity

Sofie Tapper; Nathanael Göransson; Peter Lundberg; Anders Tisell; Peter Zsigmond

doi:10.1186/s40673-020-00116-y

A pilot study of essential tremor: cerebellar GABA+/Glx ratio is correlated with tremor severity

Cerebellum Ataxias. 2020 Jun 26:7:8. doi: 10.1186/s40673-020-00116-y. eCollection 2020.

Authors

Sofie Tapper^#^{1

2}, Nathanael Göransson^#³, Peter Lundberg^{1

2}, Anders Tisell^{1

2}, Peter Zsigmond⁴

Affiliations

¹ Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.
² Department of Medical Radiation Physics and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
³ Department of Biomedical Engineering, Linköping University, Linköping, Sweden.
⁴ Department of Neurosurgery and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

^# Contributed equally.

Abstract

Objective: Essential tremor is a common movement disorder with an unclear origin. Emerging evidence suggests the role of the cerebellum and the thalamus in tremor pathophysiology. We examined the two main neurotransmitters acting inhibitory (GABA+) and excitatory (Glx) respectively, in the thalamus and cerebellum, in patients diagnosed with severe essential tremor. Furthermore, we also investigated the relationship between determined neurotransmitter concentrations and tremor severity in the essential tremor patients.

Methods: Ten essential tremor patients (prior to deep brain stimulation surgery) and six healthy controls, were scanned using a 3 T MR system. GABA+ and Glx concentrations were measured using magnetic resonance spectroscopy (MRS) performed using single voxel MEGA-PRESS. For the purpose of assessing the tremor severity, the essential tremor rating scale (ETRS) was used in accordance with Fahn, Tolosa, and Marin.

Results: We demonstrated that the cerebellar GABA+/Glx ratio was positively correlated to the ETRS (r = 0.70, p = 0.03) in essential tremor. Cerebellar and thalamic GABA+ and Glx concentrations did not show any significant difference when comparing essential tremor patients with healthy controls, at the group level.

Conclusion: We demonstrated a positive correlation between increasing tremor disability and the ratio of GABA+/ Glx in the cerebellum of essential tremor patients. This highlights the impact of an altered balance of the excitatory and inhibitory neurotransmitters in tremor severity. Rather than a change in GABA+, which was constant, we attribute this finding to an overall decrease of Glx.

Keywords: Essential tremor; GABA; Glutamate; MEGA-PRESS; Magnetic resonance spectroscopy.