Imaging shows effects of alcohol use on brain

Excessive alcohol use is one of the 10 leading causes of disease and injury in developed countries, accounting for 9.2% of the disease burden. It causes nearly one in 10 cases of ill health and premature death in Europe and is responsible for over 3% of worldwide deaths (1.8 million) every year and 4% of disability-adjusted life years lost (58.3 million). The health service in England and Wales pays up to British Sterling 1.7 billion ( Euro 2.43 billion) per annum to treat alcohol-related conditions.

Excessive alcohol use is one of the 10 leading causes of disease and injury in developed countries, accounting for 9.2% of the disease burden. It causes nearly one in 10 cases of ill health and premature death in Europe and is responsible for over 3% of worldwide deaths (1.8 million) every year and 4% of disability-adjusted life years lost (58.3 million).1 The health service in England and Wales pays up to British Sterling 1.7 billion ( Euro 2.43 billion) per annum to treat alcohol-related conditions.

Chronic alcohol use is known to exert harmful effects on a number of the body's organ systems. Those most affected include the central nervous, gastrointestinal and hepatobiliary, cardiovascular, and musculoskeletal systems. Many of the mechanisms by which alcohol affects these systems are not yet understood completely, and radiology departments can play a vital role in identifying morphologic consequences of alcohol abuse and ensuring appropriate treatment of patients.1

Imaging plays an important part in studying the neurologic consequences of alcohol abuse. Advances in MR spectroscopy, molecular imaging, and PET increasingly reveal the neural mechanisms of alcohol addiction and the biochemical changes that take place in the brain of an alcoholic patient.

Autopsy studies have shown that patients with a history of chronic alcohol consumption have smaller, lighter, more shrunken brains than adults of the same age and sex who are not alcoholic. Some studies suggest that women may be more susceptible to alcohol-related brain atrophy than men.2 CT and MR imaging have confirmed these findings repeatedly. Cross-sectional imaging techniques reveal consistent association between heavy alcohol use and morphologic brain damage, even in the absence of medical conditions previously considered to be clinical indicators of severe alcoholism, such as chronic liver disease or alcohol-induced dementia.

Imaging reveals shrinkage to be more extensive in the folded outer layer of the cerebral cortex. This is observed particularly in the frontal lobe, which is the site of higher intellectual functions. One serial imaging study of a group of alcoholic subjects, who continued drinking over a five-year period, showed progressive brain shrinkage that significantly exceeded normal age-related shrinkage. Frontal cortex shrinkage was found to be directly proportional to the amount of alcohol consumed.4

Shrinkage also occurs in deeper brain regions, including the memory and association areas, and in the cerebellum, which helps regulate coordination and balance. Cerebellar atrophy and decreased cerebellar blood flow are responsible for impaired balance and gait. Such impairment may cause falls among older alcoholic patients, leading to head injuries that can exacerbate brain dysfunction. Imaging departments see a large number of such patients every year. Some studies have found an approximate correlation between shrinkage of mammillary bodies and degree of memory loss.4

Chronic alcoholic patients may suffer from Wernicke's encephalopathy (WE), a neurologic disorder that can start abruptly or emerge over a longer time period. It is characterized by nystagmus, ocular motor palsies, unsteadiness of stance and gait, and a confused, apathetic state. Symptoms may occur in isolation, but they more often occur in various combinations. Only a minority of patients present with the classic Wernicke's triad of nystagmus, ataxia, and confusion.

Mammillary body atrophy is an irreversible marker of chronic WE that is best assessed on sagittal or coronal MRI. One group of researchers, however, has found no significant difference in the MRI prevalence of mammillary body atrophy between asymptomatic alcoholic patients and those with WE.5 Atrophy of the diencephalic or mesencephalic structures, characterized by dilatation of the third ventricle or aqueduct, may also point to a contribution of thiamine deficiency in the patient with chronic amnesia.

The characteristic MR findings in acute WE are high signal intensity on T2-weighted images in areas surrounding the third ventricle, aqueduct, and paramedian thalamic nuclei. Enhancement of mammillary bodies and the periventricular region of the third ventricle and periaqueductal area on postcontrast T1-weighted images can be observed. These findings can be resolved after thiamine supplementation. In the chronic phase of WE, T2 hyperintensity is no longer visible, but mammillary bodies and cerebellar vermis become atrophic and third ventricular enlargement is evident. High signal intensity on T2-weighted images can be resolved within 48 hours, and atrophic changes may appear as early as one week. These findings suggest a poor prognosis, even with thiamine supplementation.

WE remains a clinical diagnosis, without specific laboratory or ancillary markers. The selective vulnerability of the midline gray matter areas and their symmetric involvement allow neuroimaging to play an important ancillary role, however.

Osmotic myelinolysis is a toxic demyelinating disease seen in alcoholic, malnourished, or chronically debilitated adults. A large proportion of cases is associated with chronic alcoholism or rapid correction of hyponatremia, although the condition has also been observed in patients with normal sodium levels. The term "osmotic demyelinization syndrome" refers to pontine and extrapontine myelinolysis. A number of therapeutic options exist that can improve the prognosis of osmotic myelinolysis patients substantially.

Prompt MR scanning is increasingly facilitating antemortem osmotic myelinolysis diagnosis (Figure 1). Radiologic findings lag behind clinical observations, however, and the two do not always correlate. Unenhanced CT images are normal or demonstrate nonspecific hypodense lesions. Pontine and extrapontine lesions are hypointense on T1-weighted MRI and hyperintense on T2-weighted images. Transverse pontine fibers are most severely affected, while pyramidal tracts are usually spared. Contrast administration produces varying results, with the majority of lesions remaining unenhanced.6

The globus pallidus and putamen show high intensity on T1-weighted MRI of patients with hepatic cirrhosis. This high signal is thought to be due in part to paramagnetic substances, especially manganese. Measurements of mean Mn concentration in postmortem examinations of hepatic cirrhosis have confirmed that its deposition may cause the high signal and nerve cell death in the globus pallidus. Signal within the globus pallidus enhances in accordance with prolongation of prothrombin time on T1-weighted MRI. This finding is also seen in patients with raised portal pressure and large varices.7

Marchiafava-Bignami syndrome is a progressive neurologic disease most frequently seen in middle-aged or elderly, predominantly male, alcoholic patients (Figure 2). Acute presentation includes confusion, ataxic gait, dysarthria, and seizures, with progression to death in many cases. Other presentations include a variety of motor, sensory, and visual dysfunctions. These include apraxias and interhemispheric disconnection, which is manifested by constructional ability deficits and agraphia.

Fluid-attenuated inversion recovery (FLAIR) MR scans of patients in the acute phase show abnormal hyperintensity in the central layer of the corpus callosum. Spin-echo sequences show these same areas as having normal signal levels. Follow-up spin-echo images in the late phase demonstrate fluidlike intensity in the central layer of the corpus callosum. FLAIR MRI of patients with chronic Marchiafava-Bignami syndrome shows corpus callosal lesions as hypointense cores surrounded by hyperintense rims. This finding indicates central necrosis and peripheral demyelination.

Marchiafava-Bignami syndrome is believed to cause discontinuous affection of the corpus callosum, and bilateral cutting of the cortex outflow. In addition to central necrosis and peripheral demyelination of periventricular lesions, MRI may indicate demyelination of the corpus callosum.8,9


Functional imaging techniques such as PET and SPECT are emerging as a valuable adjunct to structural brain damage studies. Local changes in blood flow and energy metabolism, measured on either modality, help identify brain regions involved in specific sensory, motor, and cognitive functions. Such studies have revealed reduced blood flow and metabolic rates in certain brain regions of heavy drinkers, compared with those of teetotalers, even in the absence of measurable brain shrinkage. Biochemical changes and functional defects revealed by MRS and PET may reflect a decrease in the number or size of neurons or a reduction in the density of communication sites between adjacent neurons.10-12

Functional imaging reveals that alcoholic subjects have diminished metabolic activity in several frontal brain regions such as the cingulate and orbitofrontal gyri, both early (two to three weeks after detoxification) and late in withdrawal (after up to eight weeks of abstinence). These findings suggest that long-term alcohol use produces significant damage to the neurotransmitter pathways in these areas.11 Research has also implicated impaired serotonin function in the severe depression that often accompanies withdrawal.13 Functional imaging has been used to help evaluate the effects of therapeutic drugs on withdrawal-induced craving.14

Imaging techniques permit researchers to study the link between brain and behavior, particularly mechanisms of alcohol addiction, with minimal risk to patients. Dynamic brain imaging enables investigations of subjects performing intellectual tasks and experiencing various emotions before, during, and after alcohol consumption.15-16

Molecular techniques to study alcohol addiction and withdrawal include labeled ligands and MRS to monitor neurotransmitter pathway change. One of the most promising areas is the dopaminergic pathway in the brain. When dopamine cells fire, they release dopamine, and this message is transmitted by postsynaptic dopamine receptors. The dopamine D2 receptor is important in the reinforcing effects of drugs and alcohol that can lead to abuse. Radiolabeled ligands used to measure dopamine D2 receptors in addicted individuals have shown that D2 receptor availability is significantly decreased across a wide variety of types of drug addictions, and these decreases are observed both during early drug withdrawal and after protracted drug detoxification. Interestingly, dopamine D2 reductions have been documented in early-onset alcoholic individuals with family histories of alcoholism.17,18

The probability of dopamine interacting with a receptor is a function of how much dopamine is liberated in the synapse and the number of receptors available. In alcohol addicts, the dopamine cells may fire, but the chance of an interaction is reduced becaue the number of receptors is significantly lower in such an individual. The addicted person thus learns that natural reinforcers are no longer exciting or motivating, as the changes in dopamine level are not large enough to signal the individual as salient stimuli.

PET and SPECT have contributed neuroimaging studies of the GABA-benzodiazepine receptor system showing that alcoholism is associated with reduced receptor levels in the brain, particularly in the frontal cortex. These reductions may occur in the absence of detectable gray matter atrophy, even in subjects who were abstinent for some time and were cognitively and neurologically normal.19 Development of more receptor subtype selective tracers is required to enable us to better understand these metabolic changes. The opioid system is involved in mediating pleasurable effects of alcohol, and it may be related to craving and using selective labeled ligands. Some studies have found an increase in opioid receptor levels in both alcoholic subjects and opioid addicts immediately after detoxification, indicating that increases in opioid receptors may be fundamental to addiction.

MRS measurement of alcoholic subjects has been reported to show regression of brain atrophy and metabolic recovery occurring at an early stage after abstinence from chronic alcohol use. MRS findings return to normal metabolic levels within weeks after detoxification. The recovery of normal N-acetylaspartate/creatine ratios is associated with improved performance on neuropsychological tests.20 These reversible choline signal changes support the hypothesis of altered cerebral metabolism of lipids in membranes or myelin in these patients.

Such studies could lead to better treatments and preventive measures because they provide information not available on conventional imaging in early stages of addiction. The integration of conventional and molecular imaging techniques with biomedical, psychosocial, and behavioral aspects of alcoholism promises improved prevention and treatment in the future.

DR. PRABHU is a specialist registrar in general and radionuclide radiology at Bristol Royal Infirmary in Bristol, U.K.


1. Strategy Unit Alcohol Harm Reduction Project. Interim analytical report. Prime Minister's Strategy Unit, U.K., Sept. 2003.

2. National Institute on Alcohol Abuse and Alcoholism. Imaging and alcoholism: a window on the brain. Alcohol Alert No. 47 April 2000 (U.S. Department of Health and Human Services).

3. Pfefferbaum A, Sullivan EV, Mathalon DH, Kim, KO. Frontal lobe volume loss observed with magnetic resonance imaging in older chronic alcoholics. Alcohol Clin Exp Res 1997;21(3):521-529.

4. Sullivan EV, Deshmukh A, Desmond JE, et al. Cerebellar volume decline in normal aging, alcoholism, and Korsakoff's syndrome: relation to ataxia. Neuropsychology 2000;14:341-352.

5. Antunez E, Estruch R, Cardenal C, et al. Usefulness of CT and MR imaging in the diagnosis of acute Wernicke's encephalopathy. AJR 1998;171(4):1131-1137.

6. Uchino A, Yuzuriha T, Murakami M, et al. Magnetic resonance imaging of sequelae of central pontine myelinolysis in chronic alcohol abusers. Neuroradiology 2003;45(12):877-880.

7. Park NH, Park JK, Choi Y, et al. Whole blood manganese correlates with high signal intensities on T1-weighted MRI in patients with liver cirrhosis. Neurotoxicology 2003;24(6):909-915.

8. Fortman BJ, Kuszyk BS. Incidentally diagnosed Marchiafava-Bignami disease. AJR 1999;173(6):1713-1714.

9. Arbelaez A, Pajon A, Castillo M. Acute Marchiafava-Bignami disease: MR findings in two patients. AJNR 2003;24(10):1955-1957.

10. Laine TPJ, Ahonen A, Rasanen P, Tiihonen J. Dopamine transporter availability and depressive symptoms during alcohol withdrawal. Psychiatry Research (1999);90(3):153-157.

11. Volkow ND, Hitzemann R, Wang GJ, et al. Decreased brain metabolism in neurologically intact healthy alcoholics. Am J Psychiatry 1992;149(8):1016-1022.

12. Fowler JS, Volkow ND. PET imaging studies in drug abuse. Clin Toxicol 1998;36(3):163-174.

13. Heinz A, Ragan P, Jones DW, et al. Reduced central serotonin transporters in alcoholism. Am J Psychiatry 1998;155:1544-1549.

14. Catafau AM, Etcheberrigaray A, Perez de los Cobos J, et al. Regional cerebral blood flow changes in chronic alcoholic patients induced by naltrexone challenge during detoxification. J Nucl Med 1999;40(1):19-24.

15. Ingvar M, Ghatan PH, Wirsen-Meurling A, et al. Alcohol activates the cerebral reward system in man. J Stud Alcohol 1998;59(3):258-269.

16. Schreckenberger M, Amberg R, Scheurich A, et al. Acute alcohol effects on neuronal and attentional processing: striatal reward system and inhibitory sensory interactions under acute ethanol challenge. Neuropsychopharmacology 2004;29(8):1527-1537.

17. Volkow ND, Wang GJ, Maynard L, et al. Effects of alcohol detoxification on dopamine D2 receptors in alcoholics: a preliminary study. Psychiatry Res 2002;116(3):163-172.

18. Kono Y, Yoneda H, Sakai T, et al. Association between early-onset alcoholism and the dopamine D2 receptor gene. Am J Med Genet 1997;74(2):179-182.

19. Lingford-Hughes AR, Acton PD, Gacinovic S et al, Reduced levels of GABA-benzodiazepine receptor in alcohol dependency in the absence of grey matter atrophy. Br J Psychiatry 1998;173:116-122.

20. Martin B, Heinz-Gerd W, Gerd W, et al. Sequential MR imaging and proton MR spectroscopy in patients who underwent recent detoxification for chronic alcoholism: correlation with clinical and neuropsychological data. AJNR 2001;22:1926-1932.