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.

Are personality traits of juvenile myoclonic epilepsy related to frontal lobe dysfunctions? A proton MRS study.

PURPOSE: Personality traits characterized by emotional instability and immaturity, unsteadiness, lack of discipline, hedonism, frequent and rapid mood changes, and indifference toward one's disease have been associated with patients who have juvenile myoclonic epilepsy (JME). Literature data demonstrate worse seizure control and more psychosocial dysfunctions among patients with JME who have those traits. In this controlled study we performed a correlation analysis of psychiatric scores with magnetic resonance spectroscopy (MRS) values across JME patients, aiming to verify the existence of a possible relation between frontal lobe dysfunction and the prevalence of personality disorders (PDs) in JME. METHODS: Sixteen JME patients with cluster B PDs, 41 JME patients without any psychiatric disorder, and 30 healthy controls were submitted to a psychiatric evaluation and to a quantitative multivoxel MRS of thalamus; insula; cingulate gyrus; striatum; and frontal, parietal, and occipital lobes. Groups were homogeneous according to age, gender, and manual dominance. Psychiatric evaluation was performed through the Scheduled Clinical Interview for DSM-IV, Axis I and II (SCID I and II, respectively). RESULTS: A significant reduction of N-acetyl-aspartate over creatinine (NAA/Cr) ratio was observed mainly in the left frontal lobe in the JME and PD group. In addition, a significant increase in the glutamate-glutamine over creatinine GLX/Cr ratio was also observed in this referred region in the same group. DISCUSSION: These data support the hypothesis that PDs in JME could represent neuronal dysfunction and possibly a more severe form of this epileptic syndrome.

Proton magnetic resonance spectroscopy study of bilateral thalamus in juvenile myoclonic epilepsy.

PURPOSE: To investigate neuronal dysfunction in the thalami of juvenile myoclonic epilepsy (JME) by using proton magnetic resonance spectroscopy (MRS). METHODS: We performed single-voxel proton MRS over the right and the left thalami of 15 consecutive patients (10 women, 5 men) with JME (mean age 20.3 years) and 16 healthy volunteers (10 women, 6 men) (mean age 24.5 years). All patients had seizure onset in late childhood-teenage, normal neurologic examination, typical electroencephalogram (EEG) of JME and normal magnetic resonance imaging (MRI). We determined N-acetylaspartate (NAA) values and NAA over creatine-phosphocreatine (Cr) values. Mann-Whitney U-test was used to evaluate group differences. RESULTS: Group analysis showed that echo time (TE) 270 integral value of NAA over left thalamus were significantly decreased in JME patients as compared with controls (34.6033+/-15.8386; 48.0362+/-22.2407, respectively, P=0.019). Also group analysis showed that thalami NAA/Cr ratios were significantly decreased in JME patients (right side, 2.21+/-1.07; left side 2.00+/-0.72) as compared with controls (right side, 3.45+/-1.50; left side, 3.08+/-1.60; P=0.011 and P=0.030, respectively). CONCLUSION: In the previous studies, NAA values in patients with JME found that they were not statistically lower in thalami than control group. But, in our study, NAA value was found low as well. It has been known that NAA is a neuronal marker and hence it is a valuable metabolite in the neuron physiopathology. As a result, in the patients with JME we tried to support the theory that the underlying mechanism of the generalized seizures was the abnormal thalamocortical circuity, determining the thalamic neuronal dysfunction in MRS statistically.

Correlation of interictal spike-wave with thalamic glucose metabolism in juvenile myoclonic epilepsy.

The purpose of this study is to define metabolic correlates of generalized spike-wave discharges in juvenile myoclonic epilepsy. We investigated the alterations in glucose metabolism and possible correlations between the interictal epileptiform discharges and regional metabolism in patients with juvenile myoclonic epilepsy using a combined positron emission tomography/electroencephalography method. We found that the thalamic metabolism is slightly increased interictally in the patient group compared with controls. We also observed significant positive correlations between the amount of spike-wave activity and thalamic metabolism. Our results provide evidence that the thalamus has an important role in the generation of spontaneous generalized spike-wave discharges in juvenile myoclonic epilepsy.