Single-Voxel Proton Magnetic Resonance Spectroscopy of the Thalamus in Idiopathic Epileptic Dogs and in Healthy Control Dogs

Abstract

The role of magnetic resonance spectroscopy (MRS) in the investigation of brain metabolites in epileptic syndromes in dogs has not been explored systematically to date. The aim of this study was to investigate metabolites in the thalamus in dogs affected by idiopathic epilepsy (IE) with and without antiepileptic drug treatment (AEDT) and to compare them to unaffected controls. Our hypothesis is that similar to humans with generalized epilepsy and loss of consciousness, N-acetyl aspartate (NAA) would be reduced, and glutamate-glutamine (Glx) would be increased in treated and untreated IE in comparison with the control group. In this prospective case-control study, Border Collie (BC) and Greater Swiss Mountain dog (GSMD) were divided into three groups: (1) healthy controls, IE with generalized tonic-clonic seizures with (2) and without (3) AEDT. A total of 41 BC and GSMD were included using 3 Tesla single-voxel proton MRS of the thalamus (PRESS localization, shortest TE, TR = 2000 ms, NSA = 240). After exclusion of 11 dogs, 30 dogs (18 IE and 12 healthy controls) remained available for analysis. Metabolite concentrations were estimated with LCModel using creatine as reference and compared using Kruskal-Wallis and Wilcoxon rank-sum tests. The Kruskal-Wallis test revealed significant differences in the NAA-to-creatine (p = 0.04) and Glx-to-creatine (p = 0.03) ratios between the three groups. The Wilcoxon rank-sum test further showed significant reduction in the NAA/creatine ratio in idiopathic epileptic dogs under AEDT compared to epileptic dogs without AEDT (p = 0.03) and compared to healthy controls (p = 0.03). In opposite to humans, Glx/creatine ratio was significantly reduced in dogs with IE under AEDT compared to epileptic dogs without AEDT (p = 0.03) and controls (p = 0.02). IE without AEDT and healthy controls did not show significant difference, neither in NAA/creatine (p = 0.60), nor in Glx-to-creatine (p = 0.55) ratio. In conclusion, MRS showed changes in dogs with IE and generalized seizures under AEDT, but not in those without AEDT. Based upon these results, MRS can be considered a useful advanced imaging technique for the evaluation of dogs with IE in the clinical and research settings.

Keywords: MRS—1H nuclear magnetic resonance spectra; N-acetyl aspartate (NAA); canine; generalized seizures; glutamate (Glu); glutamate-glutamine (Glx); glutamine (Gln).

Figure 1

All measured spectra of the three investigated groups. In the background, the individual spectra of all dogs are plotted as outputted from LCModel (.coord files). The thicker line shows the calculated mean spectrum in each group. The spectra show a consistent quality, and the observed differences in N-acetyl aspartate (NAA) and glutamate–glutamine (Glx) in idiopathic epilepsy (IE) with antiepileptic drug treatment (AEDT) are already indicated in this visual overview.

Figure 2

Spectrum with signal-to-noise ratio of 16 (study mean: 12.9) and water peak full width at half maximum of 6.8 Hz (study mean: 6.79 Hz) of an idiopathic epileptic dog with antiepileptic drug treatment. The black line shows the acquired data, the gray area the overall fit, and the colors the individual fit components displayed for selected metabolites. Fit residuals are shown at the top. NAA, N-acetyl aspartate; NAAG, N-acetylaspartylglutamate; Glu, glutamate; Gln, glutamine; GABA, gamma-amino-butyrate.

Figure 3

Box plot of thalamic metabolite concentrations relative to creatine (A) and water (B) in healthy control dogs (red), dogs affected by idiopathic epilepsy with antiepileptic drug treatment (IE with AEDT in blue), and non-treated epileptic dogs (IE without AEDT in green). The Kruskal–Wallis test revealed statistically significant difference in the metabolites NAA/creatine and Glx/creatine, as well as tNAA/water (asterisk). Glx, glutamate–glutamine complex; tCr, total creatine; tNAA, total NAA; NAA, N-acetyl aspartate; GABA, gamma-amino-butyrate.

Figure 4

Transverse (A), sagittal (B), and dorsal (C) T1-weighted MRI images of the brain of a dog with idiopathic epilepsy showing the location of the voxel of interest in the right part of the thalamus.