Nuclear magnetic resonance spectroscopy of seizure states

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 detected in vivo seizure-induced cerebral acidosis and reduction 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 animals: (a) dissociation of brain lactate and pH during experimental status epilepticus of low and intermediate intensity, reflecting metabolic compartmentation; and (b) long persistence of metabolically active elevated brain lactate after brief cortical electroshock. The latter phenomenon may be an extreme form of a mechanism by which lactate production primes synaptic terminals for maximal sustained firing rates during normal brain activation. 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. Acidosis, reduction of phosphocreatine, and elevation of lactate have all been demonstrated in the human brain during seizure discharge. Chronic reduction of N-acetylaspartate in limbic regions probably reflects neuronal loss and may correlate with mesial temporal sclerosis.