Induced and Spontaneous Seizures in Man Produce Increases in Regional Brain Lipid Detected By in Vivo Proton Magnetic Resonance Spectroscopy

Abstract

Elevations of brain concentrations of arachidonic acid and other free fatty acids (FFAs) by seizures induced in animals were demonstrated some years ago. Similarly, large shifts of potassium (K⁺) from intra- to extracellular space during seizure activity have been documented in numerous studies. More recent studies of cell membrane function demonstrated a direct effect of FFAs on membrane K⁺ conductance, suggesting that FFAs may play a primary role in seizure evolution in brain tissue. Using electroconvulsive therapy (ECT), in which generalized seizures are induced in patients by passage of electrical current, as a controlled human model of seizures, we studied the in vivobiochemical effects of single generalized seizures with localized proton magnetic resonance spectroscopy (¹H MRS). We found that ECT reliably induces an elevation in the lipid signal that resonates at approximately 1.2 ppm. We observed a similar increase in brain lipids in a patient with temporal lobe epilepsy temporarily off medication; the signal disappeared after re-medication. Similar observations were noted for a subject with focal gliosis bordering a resected brain tumor. Finally, acute alcohol effects seem also to induce observable lipid changes. The ¹H MRS technique does not yet permit direct identification of the specific lipids involved but analysis of cerebrospinal fluid obtained by lumbar puncture before and immediately after ECT may permit more precise characterization of the observed lipid increases. Theoretical and clinical implications of these results for the study of brain FFAs and epilepsy will be discussed.