Epilepsia, zyxwvutsrqponm 35(Suppl. zyxwvutsrqpo 6):S14-S20, 1994 Raven Press, Ltd., New zyxwvutsrqp York zyxwvutsrqpon 0 International League Against Epilepsy zyxwvutsrqpo Nuclear Magnetic Resonance Spectroscopy of Seizure States James W. Prichard Department zyxwvuts of Neurology, Yale University, New Haven, Connecticut, U.S.A. Summary: Magnetic resonance spectroscopy (MRS) can be used for noninvasive measurement of more than two dozen small metabolites in the brains of living animals and humans. In the first decade of its use for study of seizure phenomena in animals, MRS successfully de- tected in vivo seizure-induced cerebral acidosis and re- duction of phosphocreatine concentration, changes that had been described previously by techniques requiring destruction of tissue. Thus validated, MRS was used to reveal new aspects of epileptic pathophysiology in ani- mals: (a) dissociation of brain lactate and pH during ex- perimental status epilepticus of low and intermediate in- tensity, reflecting metabolic compartmentation; and (b) long persistence of metabolically active elevated brain lactate after brief cortical electroshock. The latter phe- nomenon may be an extreme form of a mechanism by which lactate production primes synaptic terminals for maximal sustained firing rates during normal brain acti- vation. Diffusion-weighted imaging of rat brain has shown that status epilepticus apparently shortens the mean path length of water diffusion, a novel finding that provides new insight concerning the physical conditions under which the seizure-related chemical changes detected by MRS occur. MRS study of epileptic patients has been undertaken more recently as instruments large enough for observations on humans have become available. Acido- sis, reduction of phosphocreatine, and elevation of lactate have all been demonstrated in the human brain during seizure discharge. Chronic reduction of N-acetylaspar- tate in limbic regions probably reflects neuronal loss and may correlate with mesial temporal sclerosis. Key Words: Magnetic resonance imaging-Brain-Epilepsy-Neu- rologic manifestations-Temporal lobe-Lactic acido- sis-Status epilepticus. Magnetic resonance spectroscopy (MRS) is a phrase used in the biomedical world to denote nu- clear magnetic resonance (NMR) observation of signals from compounds other than water. Liter- ally, all. NMR measurements are spectroscopy, but the NMR signal from water protons is so much stronger than other signals obtainable from living tissue that observations based on it found biomed- ical applications sooner and came to be known col- lectively as magnetic resonance imaging (MRI). MRI has been used extensively for diagnosis and research in epilepsy, as described elsewhere in this volume. The subject of this article is MRS research based on observations of 31P, 'H in compounds other than water, I3C, and 23Na.All of these signals are much weaker than the 'H water signal. In consequence, Address correspondence and reprint requests to Dr. J. W. Prichard at Department of Neurology. Yale University, 333 Ce- dar Street, New Haven, CT 06510, U.S.A. recording them takes longer, and anatomic resolu- tion in human subjects is usually a centimeter or more rather than a millimeter or less as in MRI. The great advantage of MRS is chemical specificity. Sig- nals from more than two dozen compounds can be detected in brain spectra from experimental animals and humans. Further development is likely to ex- tend this capability considerably beyond its present (late 1993) stage. As its technology matures, MRS can be expected to supply an abundance of unique information on the biochemistry of normal and pathologic neurobiological processes. The informa- tion will be especially useful because the noninva- sive means of obtaining it allows observations to be made as often as needed on the same subject. Chemically specific longitudinal studies of develop- ment and disease in the brain will become common- place. In the decade since the first in vivo MRS obser- vations of a seizure state were made (Prichard et al., 1983), several aspects of epileptic pathophysi- z s14