Effect of Primidone on Dentate Nucleus γ-Aminobutyric Acid Concentration in Patients With Essential Tremor

Abstract

Objectives: It is not known whether current use of the medication primidone affects brain γ-aminobutyric acid (GABA) concentrations. This is an important potential confound in studies of the pathophysiology of essential tremor (ET), one of the most common neurological diseases. We compared GABA concentrations in the dentate nucleus in 6 ET patients taking primidone versus 26 ET patients not taking primidone.

Methods: (1)H magnetic resonance spectroscopy was performed using a 3.0-T Siemens Tim Trio scanner. The MEGA-PRESS J-editing sequence was used for GABA detection in 2 cerebellar volumes of interest (left and right) that included the dentate nucleus.

Results: The right dentate GABA concentration was similar in the 2 groups (2.21 ± 0.46 [on primidone] vs 1.93 ± 0.39 [not on primidone], P = 0.15), as was the left dentate GABA concentration (1.61 ± 0.35 [on primidone] vs 1.67 ± 0.34 [not on primidone], P = 0.72). The daily primidone dose was not associated with either right or left dentate GABA concentrations (P = 0.89 and 0.76, respectively).

Conclusions: We did not find a difference in dentate GABA concentrations between 6 ET patients taking daily primidone and 26 ET patients not taking primidone. Furthermore, there was no association between daily primidone dose and dentate GABA concentration. These data suggest that it is not necessary to exclude ET patients on primidone from magnetic resonance spectroscopy studies of dentate GABA concentration, and if assessment of these concentrations was to be developed as a biomarker for ET, primidone usage would not confound interpretation of the results.

Figure 1

Top: Representative GABA-edited spectrum from the dentate VOI showing the raw data and the LCModel fit. Bottom: Placement of the GABA VOI, containing the left cerebellar dentate.

Figure 2

GABA concentrations in the right dentate nuclei in ET patients on vs. off primidone (gray bars) and GABA concentrations in the left dentate nucleus in ET patients on vs. off primidone (black bars). Bars represent means and one standard deviation.