Chemical pathology in brain white matter of recently detoxified alcoholics: A H-1 magnetic resonance spectroscopy investigation of alcohol-associatedfrontal lobe injury

Background: Investigations have suggested that frontal lobe abnormalities a re a prominent feature of the alcoholic brain, indicated by impaired neurop sychological performance on tests of frontal lobe function and by reduced f rontal lobe volume in neuroimaging and neuropathological examinations. Whit e matter compartment volume loss may underlie observed brain shrinkage and cognitive deficits associated with the frontal lobes, although the nature o f this change has not been well-characterized, Method: To investigate the susceptibility of frontal lobe white matter to a lcohol-associated metabolic change and to understand the nature of alcohol- related white matter injury,H-1 magnetic resonance spectroscopy (MRS) was u sed to measure concentrations of metabolites in frontal white matter (FWM) and parietal white matter (PWM) of recently detoxified alcoholics (RDA) and nonalcoholic controls (CON). Concentrations of N-acetylaspartate (NAA), ch oline-containing compounds (Cho), myo-inositol (Ins), and creatine plus pho sphocreatine (Cr) were measured in 37 RDA (mean age, 40.4 years; mean lengt h of abstinence, 27.9 days) and 15 CON (mean age, 38.0 years). Results: Analysis of variance (ANOVA) revealed a group by region of interes t interaction for concentrations of NAA. Simple effects analysis revealed a significant 14.7% reduction in FWM NAA, while NAA levels in PWM were simil ar in RDA and CON. In addition, RDA had an 11.8% increase (averaged across both regions of interest) in brain white matter Ins relative to CON. Reduct ions in FWM NAA were associated with a longer drinking history in the RDA g roup, but this result was not found when both age and drinking history were used to predict the level of FWM NAA. Conclusions: Alcohol-associated reductions in FWM NAA may be the result of neuronal loss or dysfunction in the metabolism of NAA. While alcohol-induce d oxidative stress may cause global brain impairments in the metabolism and subsequent reduction of NAA, the frontal lobes are particularly rich in ex citatory amino acid pathways, and axonal damage or destruction secondary to glutamate-mediated excitotoxicity during alcohol withdrawal may cause fron tal lobe-specific reductions in NAA. Elevations in brain white matter Ins m ay reflect astrocyte proliferation as well as an osmotic response to cell s hrinkage.