Syllabus

In 2012, 3.3 million (6%) worldwide deaths were attributable to alcohol consumption. Globally, alcohol misuse is the fifth leading risk factor for premature death and disability; among those aged 15 - 49 years, it is the first (1). It is therefore critical for clinicians to be attentive of the scope of the problem and consider the extent of alcohol use in all patients. Since heavy alcohol use has been shown to affect brain imaging metrics (including brain volume, MRS-detectable metabolites, and diffusion tensor imaging measures), awareness of the effects of alcohol on the brain is also critical for all personnel involved with brain MR imaging. Those who attend this lecture will get an overview of alcohol-related diseases that have clear neuroimaging signature. They will also gain a better understanding of the permanent and transient effects of alcohol misuse on brain structural integrity. This information will also apprise researchers of the importance of interrogating volunteers about drinking consumption recency, frequency, and amount before assuming that a volunteer is truly an "unaffected healthy participant." In support of postmortem neuropathological studies showing degeneration of white matter, neuroimaging studies have shown a specific vulnerability of regional white matter macrostructure using conventional MRI and microstructure using diffusion tensor imaging (DTI) to chronic alcohol exposure. Such studies have demonstrated white-matter volume deficits that typically affect anterior brain systems. Gray matter tissue is also affected in chronic alcoholism where frontal, parietal, and cerebellar systems are commonly affected. Unlike many disorders affecting brain structure, prolonged sobriety can result in gray matter volume expansion and improvement in microstructural measures of white matter fiber tract integrity. Because of the potential for at least partial reversal of tissue volume deficits, it is preferable to characterize deficits as shrinkage rather than loss, which denotes a permanent condition. In order to evaluate its central nervous system (CNS) effects, researchers distinguish “uncomplicated alcoholism” from the various clinically diagnosable consequences of chronic alcohol consumption, including Wernicke’s encephalopathy (WE), Korsakoff’s syndrome (KS), [Wernicke-Korsakoff syndrome (WKS) is used to refer to the presence of both WE and KS because WE is a common antecedent to KS], hepatic encephalopathy (HE), central pontine myelinolysis (CPM), and Marchiafava–Bignami disease (MBD). The evaluation of clinically defined syndromes associated with chronic alcoholism, each with a relatively unique radiologic signature, provides guideposts for the interrogation of the brain in uncomplicated alcoholism. Human studies offer a full depiction of the consequences of chronic alcohol exposure but are limited by ethical considerations. That is, rigorous experimentation requires the ability to control for relevant variables such as the premorbid condition of the brain. The wide variation (or heterogeneity) of alcoholic populations examined with respect to genetic predisposition, age of onset, pattern of drinking, frequency of withdrawals, length of sobriety, nutritional, and hepatic status has hampered systematic attempts to isolate specific brain regions and mechanisms affected by alcohol, per se. This heterogeneity, and the complexity that it introduces, makes characterizing the disorder a research challenge. Animal models, in contrast to the indefinite natural course of alcohol use in humans, allow researchers to determine alcohol toxicity by controlling multiple genetic, environmental, sex, and alcohol consumption factors. Animal models permit the study of underlying mechanisms, thereby enhancing interpretations of findings in human studies DTI results from alcoholics with WKS (2, 3), HE (4-8), CPM (9, 10), and MBD (11-16) will be reviewed. DTI has revealed microstructural damage related to alcoholism in CNS areas that appear intact in structural MRI analyses (17-19). These results will be discussed. DTI data have been collected in animal models of WE (20-22). In one study, animals with WE induced by thiamine deficiency were imaged at baseline, presymptomatic stage (day 10), symptomatic stage (days 12 and 14), and after recovery on days 31 and 87. A decrease in fractional anisotropy (FA) in the inferior colliculi was first noted on day 10 but showed recovery on day 87. On the other hand, the FA decrease in the thalamus first noted on day 12 persisted through day 87. Affects of various ethanol (EtOH) exposure protocols on rat brain DTI metrics will be covered (23-25). For example, adult rats exposed to a single dose of EtOH showed a slight and transient reduction, relative to unexposed rats, in apparent diffusion coefficient in brainstem (23), frontal lobe, hippocampus, thalamus, and cerebellum (24). Binge EtOH followed by a week of sobriety resulted in rapidly reversible decreases in FA in callosal genu and fimbria-fornix but not splenium; and increases in mean diffusivity selective to the fimbria-fornix (25).

Acknowledgements

No acknowledgement found.

References

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