Nuclear Magnetic Resonance Spectroscopy of Seizure States

Abstract

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.

Magnetic resonance spectroscopy in Alzheimer's disease: focus onN-acetylaspartate

“…NAA is also reduced in diseases that affect the central nervous system. Studies have documented relatively low NAA levels in hypoxic encephalopathy (31), human immuno‐deficiency virus (32), multiple sclerosis (33), traumatic brain injury, schizophrenia (34, 35), Huntington's disease (36), Huntington gene carriers, epilepsy (37, 38), mild cognitive impairment (MCI) as well as AD. The AD studies are reviewed in greater detail in a subsequent section.…”

Some methodological issues in neuroradiological research in psychiatry

“…Acidosis, reduction of phosphocreatine, and lactate elevation have all been demonstrated in the human brain during seizure discharge. Chronic NAA reduction in limbic regions probably reflects neuronal loss and may correlate with mesial temporal sclerosis (Prichard, 1994).…”

Magnetic Resonance Spectroscopy in Animal Models of Epilepsy

“…The predominant nonwater proton‐containing metabolites in brain that can be detected simultaneously at an echo time of 135 ms by proton ( 1 H) MRS include N ‐acetylaspartate (NAA), choline (Cho), creatine (Cr), and lactate. As the water signal on 1 H MRS is > 10,000 times more intense than other molecules, water‐suppressed 1 H MRS techniques, such as the CHESS (Chemical Shift Selective) RF pulse, have been developed to obtain spectra from selected regions within the brain (Bottomley et al, 1984; Frahm et al, 1989; Moonen et al, 1989; Prichard, 1994). Chemical shift imaging (CSI) is an alternative to the analysis of a single region of interest at a given time by permitting the simultaneous acquisition of spectra from multiple areas of the brain, known as voxels of interest (VOI).…”

“…When applied to animal models, MRS has allowed a detailed look at the biochemistry involved in epileptic states in viv o (Prichard, 1994). Animal models of epilepsy allow the testing of the effects of therapeutic interventions, and most importantly, to identify the basic mechanisms of epilepsy itself (Fisher, 1989; Engel, 1992; Prichard, 1994).…”

“…When applied to animal models, MRS has allowed a detailed look at the biochemistry involved in epileptic states in viv o (Prichard, 1994). Animal models of epilepsy allow the testing of the effects of therapeutic interventions, and most importantly, to identify the basic mechanisms of epilepsy itself (Fisher, 1989; Engel, 1992; Prichard, 1994). MRS allows the study of such mechanisms, in addition to the detection and the semiquantification of more than two dozen compounds, with very little risk of harmful side effects, and has the unique quality of replication (Prichard, 1994).…”