Frontal and thalamic changes of GABA concentration indicate dysfunction of thalamofrontal networks in juvenile myoclonic epilepsy.

OBJECTIVE: Juvenile myoclonic epilepsy (JME) has been considered to be a frontal variant of thalamocortical network dysfunction in epilepsy. Changes of γ-aminobutyric acid (GABA)ergic neurotransmission may play a key role in this dysfunction. Magnetic resonance spectroscopy (MRS) is the only noninvasive method to measure GABA concentrations in different brain regions. We measured GABA and other metabolite concentrations in the thalamus and frontal lobe of patients with JME. METHODS: A specific protocol was used for determining GABA concentrations in the thalamus, frontal lobe, and motor cortex contralateral to the handedness in 15 patients with JME and 15 age-matched controls. In addition, we measured concentrations of glutamate and glutamine, N-acetyl-aspartate (NAA), myoinositol, creatine, and choline using MRS with short echo time. JME-related concentration changes were analyzed comparing patients to controls, also considering potential effects of antiepileptic drugs. RESULTS: In patients with JME, GABA and NAA were reduced in the thalamus (p = 0.03 and p = 0.02), whereas frontal GABA and glutamine were elevated (p = 0.046 and p = 0.03). MRS revealed reduced NAA in the thalamic gray matter contralateral to the handedness (p = 0.04 each). These changes were found consistently in patients treated with new antiepileptic drugs and with valproate, although the extent of metabolic changes differed between these treatments. SIGNIFICANCE: Decreased thalamic and increased frontal GABA suggest a dysfunction of GABAergic neurotransmission in these brain regions of patients with JME. The NAA decrease in the gray matter of the thalamus may hint to a damage of GABAergic neurons, whereas frontal increase of GABA and its precursor glutamine may reflect increased density in GABAergic neurons due to subtle cortical disorganization in the thalamofrontal network.

Metabolic gray matter changes of adolescents with anorexia nervosa in combined MR proton and phosphorus spectroscopy.

INTRODUCTION: There are hints for changes in phospholipid membrane metabolism and structure in the brain of adolescents with anorexia nervosa (AN) using either proton ((1)H) or phosphorus ((31)P) magnetic resonance spectroscopic imaging (MRSI). We aimed to specify these pathological metabolite changes by combining both methods with additional focus on the neuronal metabolites glutamate (Glu) and N-acetyl-l-aspartate (NAA). METHODS: Twenty-one female patients (mean 14.4 ± 1.9 years) and 29 female controls (mean 16 ± 1.6 years) underwent (1)H and (31)P MRSI at 3 T applied to the centrum semiovale including the anterior cingulate cortex. We assessed gray matter (GM) and white matter (WM) metabolite concentration changes of the frontal and parietal brain measuring choline(Cho)- and ethanolamine(Eth)-containing compounds, Glutamate (Glu) and glutamine (Gln) and their sum (Glx), myoinositol, NAA, and high-energy phosphates. RESULTS: For (1)H MRSI, a clear discrimination between GM and WM concentrations was possible, showing an increase of Glx (p < 0.001), NAA (frontal p < 0.05), pooled creatine (tCr) (p < 0.001), and choline (tCho) (p < 0.05) in the GM of AN patients. The lipid catabolites glycerophosphocholine (p < 0.07) and glycerophosphoethanolamine (p < 0.03) were increased in the parietal region. CONCLUSIONS: Significant changes in GM metabolite concentrations were observed in AN possibly triggered by elevated excitotoxin Glu. Increased tCho may indicate modifications of membrane phospholipids due to increased catabolism in the parietal region. Since no significant changes in phosphorylated choline compounds were found for the frontal region, the tCho increase in this region may hint to fluidity changes.