title: Frontal and thalamic changes of GABA concentration indicate dysfunction of thalamofrontal networks in juvenile myoclonic epilepsy.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neuroradiology, Goethe University Frankfurt, Frankfurt, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Hattingen
authors.forename: Christian
authors.initials: C
authors.lastname: Lückerath
authors.forename: Stefanie
authors.initials: S
authors.lastname: Pellikan
authors.forename: Dmitri
authors.initials: D
authors.lastname: Vronski
authors.forename: Christine
authors.initials: C
authors.lastname: Roth
authors.forename: Susanne
authors.initials: S
authors.lastname: Knake
authors.forename: Matthias
authors.initials: M
authors.lastname: Kieslich
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pilatus
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D005625:Frontal Lobe / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020190:Myoclonic Epilepsy, Juvenile / Q000175:diagnosis* / Q000378:metabolism* / Q000503:physiopathology; D009415:Nerve Net / Q000378:metabolism* / Q000503:physiopathology; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D011446:Prospective Studies; D013788:Thalamus / Q000378:metabolism* / Q000503:physiopathology; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid
keywords: GABA; Juvenile myoclonic epilepsy; MR spectroscopy; Thalamofrontal