Abstracts

Rationale: The neuroanatomical basis and the neurochemical abnormalities that underlay juvenile myoclonic epilepsy (JME) are not fully defined. While the thalamus plays a central role in synchronization of widespread regions of the cerebral cortex during a seizure, emerging evidence suggests that all cortical neurons may not be homogeneously involved. The purpose of this study was to investigate the cerebral metabolic differences between JME patients (JME-P) and normal controls (CTL) and to evaluate to what extent these abnormalities reflect involvement of an epileptic network. Methods: All patients had a JME diagnosis based on seizure history and semiology, normal high-resolution MR and interictal ± ictal video-EEG. Sixty JME-P with a median age of 26 (range 14-55) years were submitted to 1.5 T MRI proton spectroscopy (1H-MRS), multi-voxel with PRESS sequence (TR/TE = 1500/30 ms) over the following locations: medial prefrontal cortex (MPC), primary motor cortex (PMC), thalamus, striatum, posterior cingulate gyrus (PCG), insular, parietal and occipital cortices. We determined ratios for integral values of N-acetyl-aspartate (NAA) and glutamine-glutamate (GLX) over creatine-phosphocreatine (Cr). The CTL consisted of 30 age and sex-matched healthy volunteers. Results: The NAA/Cr ratio was reduced on PMC (2.20 vs. 2.43; p = 0.011), MPC (2.08 vs. 2.26; p = 0.012) and thalamus (1.91 vs. 2.24; p = 0.012) among JME-P. Also, JME-P had altered GLX/Cr ratio, on PMC (0.37 vs. 0.53; p = 0.013), MPC (0.35 vs. 0.49; p = 0.028) and PCG (0.50 vs. 0.67; p = 0.042), where it was reduced, while it was increased on insula (0.48 vs. 0.32; p = 0.012), striatum (0.31 vs. 0.16; p = 0.002) and thalamus (0.33 vs. 0.22; p = 0.084). Multiple regression analysis revealed the strongest correlation between thalamus and MPC (45.9%), but the thalamus was also correlated with insula (29.1%), occipital cortex (29.0%) and striatum (27.7%) among JME-P. Lower NAA/Cr was observed with advancing age and duration of epilepsy, regardless of frequency of seizures and antiepileptic drug therapy in thalamus and frontal cortex. Conclusions: The identification of a specific network of neurochemical dysfunction among JME-P, with diverse involvement of particular structures within the thalamocortical circuitry, suggests that cortical hyperexcitability in JME is not necessarily diffuse, supporting the knowledge that the focal/generalized distinction of epileptogenesis should be reconsidered. Reductions in NAA may represent loss or injury of neurons and/or axons, as well as metabolic dysfunction while glutamate is considered to be an excitatory neurotransmitter in the brain which is involved in the pathogenesis of epileptogenic seizures. At last, the alterations found in NAA/Cr seem worsened with increasing duration of epilepsy, while it was not related to the clinical control of seizures. It supports the idea that neuronal dysfunction in JME could be primarily related to the underlying epileptogenic process rather than to the effect of the seizures themselves.