Valproate-induced metabolic changes in patients with epilepsy: assessment with H-MRS.
OBJECTIVE
Valproate (VPA) interferes with mitochondrial metabolism causing hyperammonemia, thereby shifting the balance reaction of glutamine (Gln)/glutamate (Glu) toward Gln. In this study we wanted to determine whether metabolic changes could be reproduced in VPA-treated patients with epilepsy and whether the results differed from those known in chronic hepatic encephalopathy (CHE).


METHODS
Seven patients with epilepsy pretreated with VPA and seven healthy volunteers were investigated on a 3T-scanner. We performed proton magnetic resonance spectroscopy ((1)H-MRS) using a short echo time point-resolved spectroscopy (PRESS) in the parietal and occipital lobe, respectively. Spectral analysis was performed by LCModel, allowing a separation of Glu and Gln at 3T. Absolute values of myo-Inositol (mI), choline (Cho), creatine (Cr), N-acetyl-aspartate (NAA), glutamine (Gln), glutamate (Glu), and the sum of Gln and Glu (Glx) were calculated.


RESULTS
In the parietal lobe, mI was significantly decreased in the patients' group compared to the healthy volunteers. After separation of the signals of Gln and Glu, a significant increase of Gln was observed in the parietal lobe in the patients' group. No significant differences in the occipital spectra could be observed between the groups.


CONCLUSIONS
In VPA-treated patients the alteration of the Glu/Gln ratio differs from that in patients with CHE, where Glx is markedly increased because of an increase in Gln. The expected shift from the biochemical balance reaction of Gln/Glu induced by VPA could be reproduced for the parietal lobe. Significantly reduced mI in the parietal lobe of VPA-treated patients most likely reflects an osmolytic compensation for high Gln.
Garcia
Meritxell
M
Department of Neuroradiology, University Hospital Erlangen, Erlangen, Germany. meritxell.garcia@uk-erlangen.de
Huppertz
Hans-Juergen
HJ
Ziyeh
Sargon
S
Buechert
Martin
M
Schumacher
Martin
M
Mader
Irina
I
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D004831:Epilepsies, Myoclonic / Q000188:drug therapy*; D004828:Epilepsies, Partial / Q000188:drug therapy*; D004830:Epilepsy, Tonic-Clonic / Q000188:drug therapy*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D022124:Hyperammonemia / Q000139:chemically induced; D007091:Image Processing, Computer-Assisted; D007294:Inositol / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009778:Occipital Lobe / Q000187:drug effects*; D010296:Parietal Lobe / Q000187:drug effects*; D012016:Reference Values; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use; D055815:Young Adult
D000927:Anticonvulsants; D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D007294:Inositol; D014635:Valproic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline