Global–Local Interference is Related to Callosal Compromise in Alcoholism: A Behavior-DTI Association Study

Background: Visuospatial ability is a multifactorial process commonly impaired in chronic alcoholism. Identification of which features of visuospatial processing are affected and which are spared in alcoholism, however, has not been clearly determined. We used a global–local paradigm to assess component processes of visuospatial ability and MR diffusion tensor imaging (DTI) to examine whether alcoholism‐related microstructural degradation of the corpus callosum contributes to disruption of selective lateralized visuospatial and attention processes. Methods: A hierarchical letter paradigm was devised, where large global letters were composed of small local letters. The task required identification of target letters among distractors presented at global, local, both, or neither level. Attention was either selectively directed to global or local levels or divided between levels. Participants were 18 detoxified chronic alcoholics and 22 age‐matched healthy controls. DTI provided quantitative assessment of the integrity of corpus callosal white matter microstructure. Results: Alcoholics generally had longer reaction times than controls but obtained similar accuracy scores. Both groups processed local targets faster than global targets and showed interference from targets at the unattended level. Alcoholics exhibited moderate compromise in selectively attending to the global level when the global stimuli were composed of local targets. Such local interference was less with longer abstinence. Callosal microstructural integrity compromise predicted degree of interference from stimulus incongruency in the alcoholic group. This relationship was not observed for lateral or third ventricular volumes, which are measures of nonspecific cortical volume deficits. Conclusion: Global–local feature perception was generally spared in abstinent chronic alcoholics, but impairments were observed when directing attention to global features and when global and local information interfered at stimulus or response levels. Furthermore, the interference‐callosal integrity relationship in alcoholics indicates that compromised visuospatial functions include those requiring bilateral integration of information.     

Thinning of the Corpus Callosum in Older Alcoholic Men: A Magnetic Resonance Imaging Study

A brain image averaging technique was applied to three-dimensional magnetic resonance images to identify visually detectable brain volume abnormalities in chronically alcoholic men, compared with healthy control men. This technique, which was based on pixel-by-pixel statistical probability mapping, revealed a dramatic reduction in the area of the corpus callosum in older alcoholics (age 45 years or older), relative to age-matched controls. Subsequent analysis used anatomical landmarks to outline the borders of midsagittal sections of the corpus callosum in a larger group of alcoholics and controls, who spanned the adult age range from 23 to 71 years. This analysis revealed significant reduction, most prominent in the genu and body, of total callosal area in the alcoholic group relative to the control group; the results were the same whether raw area measures or head size plus age adjusted measure were analyzed. Significant thinning of the callosal body in alcoholics is usually attributed to the relatively rare, nutritional-deficient condition, Marchiafava-Bignami disease. However, callosal thinning was present in vivo in chronic alcoholics without clinical symptoms of severe liver disease, amnesia, or alcoholic dementia. These data suggest that chronic alcoholism can be characterized by a continuum of graded brain dysmorphology, rather than classical alcoholic-related subsyndromes, such as Marchiafava-Bignami disease.     

Relationship between Alcohol Withdrawal Seizures and Temporal Lobe White Matter Volume Deficits

A previous magnetic resonance imaging study from our laboratory reported significant temporal lobe volume deficits in cortical gray matter, white matter, and anterior hippocampus in chronic alcoholic men relative to controls. In the present study, we reexamined these data and asked whether withdrawal seizure history was predictive of either the hippocampal or the extrahippocampal volume deficits. A review of the medical charts indicated that 11 alcoholics had experienced one or more alcohol-related seizures and 35 were seizure-free; no patient had a seizure disorder unrelated to alcohol. The two alcoholic groups did not differ significantly in age, education, alcohol consumption variables, premorbid intelligence, Memory Quotient, Trail Making, or detection of hidden figures. Although each alcoholic group showed significant bilateral volume deficits of the anterior hippocampus and frontal-parietal and temporal gray matter, relative to controls, the seizure group had significantly smaller temporal lobe white matter volumes than either the control or the seizure-free groups; the latter two groups did not differ from each other. Both alcoholic groups, however, had white matter volume deficits in the frontal-parietal region. Thus, the seizure group accounted for the white matter volume deficits in the temporal lobe previously reported in the full sample of alcoholics. It seems, then, that reduced white matter volume in the temporal lobes may be either a risk factor for or sequela of alcohol withdrawal seizures.     

Cerebral white matter lesions in primary Sj?gren's syndrome: a controlled study.

OBJECTIVE: To determine the prevalence of neurological and magnetic resonance imaging (MRI) abnormalities in a well defined population of unselected patients with primary Sj?gren's syndrome (SS) and age and sex matched healthy patients. METHODS: Thirty patients with SS and 29 age and sex matched controls were examined by a neurologist and subsequently underwent MRI scanning with a 1.0 Tesla Siemens Impact MR scanner. Scans were graded by a neuroradiologist blinded to the clinical status of each subject. The number and location of white matter lesions > 3 mm in long axis (to exclude non-specific perivascular changes) were recorded for each subject. RESULTS: There was a significant increase in lesions detected by MRI in SS patients versus controls (p = 0.02) including deep white matter lesions (p = 0.03) and subcortical white matter lesions (p = 0.02). The presence of white matter lesions did not correlate with serum IgG or rheumatoid factor levels, or with presence of anticardiolipin antibodies. No subjects had symptoms or signs of serious neurological disease including multiple sclerosis, and corpus callosal lesions commonly seen in multiple sclerosis were notably absent in this study. CONCLUSION: Cerebral white matter lesions detected by MRI are more frequent in patients with primary SS than control subjects, yet do not appear to be associated with significant clinical manifestations. Although the pathological nature of these lesions is yet to be defined, their presence should not be over-interpreted.     

Longitudinal Changes in Magnetic Resonance Imaging Brain Volumes in Abstinent and Relapsed Alcoholics

Chronic alcoholism is associated with smaller volumes of cortical gray matter and white matter and a complementary increase in brain cerebrospinal fluid (CSF) volumes, relative to age norms. This longitudinal study quantified the extent of brain volume changes associated with abstinence and drinking at three time points in chronic alcoholics. We obtained magnetic resonance imaging (MRI) on 58 alcoholic men after an average of 12 days (MRI-1) and 32 days (MRI-2) of sobriety. In addition, 58 healthy control subjects were scanned at a comparable interval. At MRI-3, 11 controls and 39 alcoholics were rescanned, 2–12 months after MRI-2; 19 alcoholics had abstained, and 20 had resumed drinking. Axial MRI slices were segmented into cortical gray matter, white matter, and CSF and summed over seven slices; lateral and third ventricular volumes were also estimated. MRI volume changes were corrected using an estimate of interscan measurement error caused by head positioning differences, and then divided by the interval to yield rates of change (slopes). From MRI-1 to MRI-2, the alcoholic group showed declines in CSF volumes of the lateral ventricles and posterior cortical sulci, and a trend toward an increase in anterior cortical gray matter volume relative to the control group. From MRI-2 to MRI-3, third ventricular volumes decreased in the abstainers relative to the relapsers and controls; cortical white matter volume decreased in the relapsers. In the relapsers, lifetime consumption of alcohol (as of MRI-1) predicted later vulnerability to white matter volume decline and third ventricular enlargement with resumption of drinking. These data suggest that improvement in cortical gray matter, sulcal, and lateral ventricular volumes occur early in the course of abstinence, and that improvement in third ventricular volume appears later with continued abstinence. Resumption of drinking after a short period of abstinence arrests third ventricular volume improvement and produces white matter volume loss.     

Corpus callosum, pons, and cortical white matter in alcoholic women

BACKGROUND: To measure the effect of alcohol abuse on white matter brain macrostructure in women with alcoholism and to determine whether observed abnormalities interact with age. METHODS: Quantitative measures of corpus callosum area, cortical white matter volume, and pons volume were derived from magnetic resonance imaging scans obtained from 34 women with DSM-III-R alcoholism (aged 28-64, mean 41 years) and 35 healthy women (aged 22-65, mean 42 years). Transverse relaxation time of the pons was also obtained. RESULTS: No significant group differences in any brain measures were observed. However, in alcoholics greater length of sobriety was associated with more cortical white matter, and higher lifetime levels of alcohol consumption were associated with smaller volumes and prolonged transverse relaxation time in the pons. CONCLUSIONS: Despite a lack of overall deficits in white matter macrostructural size in alcoholic women, certain white matter structures showed alcohol exposure vulnerability whereas others showed evidence of recovery with abstinence.     

Transcallosal White Matter Degradation Detected With Quantitative Fiber Tracking in Alcoholic Men and Women: Selective Relations to Dissociable Functions

Introduction: Excessive alcohol consumption can adversely affect white matter fibers and disrupt transmission of neuronal signals. Here, we examined six anatomically defined transcallosal white matter fiber bundles and asked whether any bundle was specifically vulnerable to alcohol, what aspect of white matter integrity was most affected, whether women were more vulnerable than men, and whether evidence of compromise in specific bundles was associated with deficits in balance, sustained attention, associative learning, and psychomotor function, commonly affected in alcoholics. Methods: Diffusion tensor imaging quantitative fiber tracking assessed integrity of six transcallosal white matter bundles in 87 alcoholics (59 men, 28 women) and 88 healthy controls (42 men, 46 women). Measures included orientational diffusion coherence (fractional anisotropy, FA) and magnitude of diffusion, quantified separately for axial (longitudinal; λL) and radial (transverse; λT) diffusivity. The Digit Symbol Test and a test of ataxia were also administered. Results: Alcoholism negatively affected callosal FA and λT of all but the sensory‐motor bundle. Women showed no evidence for greater vulnerability to alcohol than men. Multiple regression analyses confirmed a double dissociation: higher diffusivity in sensory‐motor and parietal bundles was associated with poorer balance but not psychomotor speed, whereas higher diffusivity in prefrontal and temporal bundles was associated with slower psychomotor speed but not balance. Conclusions: This study revealed stronger alcohol effects for FA and radial diffusivity than axial diffusivity, suggesting myelin degradation, but no evidence for greater vulnerability to alcohol in women than men. The presence of brain‐behavior relationships provides support for the role of alcoholism‐related commissural white matter degradation as a substrate of cognitive and motor impairment. Identification of a double dissociation provides further support for the role of selective white matter integrity in specific domains of performance.     

Brain Gray and White Matter Volume Loss Accelerates with Aging in Chronic Alcoholics: A Quantitative MRI Study

Magnetic resonance imaging (MRI) was used to study in vivo the brains of 49 patients with chronic alcoholism, 3 to 4 weeks post-withdrawal, and 43 normal healthy controls, all right-handed male veterans between the ages of 23 and 70 years. MRI scans were analyzed using a semi-automated procedure, which allowed the subcortical regions to be segmented into cerebrospinal fluid (CSF) and brain tissue and the cortical regions to be segmented into CSF, gray matter, and white matter. An age regression model was used to examine the effects of alcohol on brain structure, over and above that expected from the normal aging process. The alcoholics exhibited decreased tissue and increased CSF after correcting for aging. In the cortex, there was significant loss of both gray matter and white matter volume. In this sample of alcoholics, no particular cortical region was preferentially affected or spared. Furthermore, brain tissue volume loss increased with advanced age in the alcoholics. In this group of alcoholics there was no relationship between length of illness and age, i.e., the younger alcoholics had as heavy alcohol use histories as did the older alcoholics. Thus, the increased brain tissue loss with advanced age is interpreted as evidence for age-related increase in brain vulnerability to chronic alcohol abuse.     

Cortical gray matter loss in treatment-naïve alcohol dependent individuals

Background: Most studies of the impact of alcohol dependence on the brain have examined individuals in treatment. Such samples represent a small proportion of alcoholics in the general population. Such samples may embody a bias (Berkson's fallacy) if the association between variables (for example, alcoholism and cortical gray matter loss) differs between the population of alcoholics in treatment and alcoholics in the general population. Our objective was to determine if treatment‐naïve alcoholics show structural brain changes versus controls and to compare our findings with reports evaluating alcoholic samples drawn from treatment populations. Methods: Structural MRI was used to assess whole brain and regional volumes of cortical gray matter and white matter in 24 young to middle‐aged treatment‐naïve alcohol‐dependent males versus 17 controls. Results: Cortical gray matter volumes in alcohol‐dependent individuals were negatively associated with age and lifetime duration of alcohol use (which were highly confounded). These subjects showed reduced whole brain (p < 0.05), prefrontal (p < 0.01), and parietal (p < 0.05) cortical gray matter compared with controls. White matter and temporal cortex, tissues that usually show volume reductions in samples drawn from treatment, did not differ between treatment‐naïve alcoholics and controls (all p > 0.40). Conclusions: Our findings are consistent with the hypothesis that structural brain changes in treatment‐naïve alcoholics are less severe than those reported in clinical samples of alcoholics, perhaps due to less concomitant psychopathology and a reduced severity of alcoholism in treatment‐naïve alcoholics. However, caution must be taken when comparing our findings with results from clinical samples, as we did not directly compare treatment‐naïve alcoholics with treated alcoholics and our treatment‐naïve sample tended to be younger than the (clinical) samples reported in the literature. Nevertheless, we suggest that most of the reports of the central nervous system consequences of alcoholism may not accurately describe the majority of alcoholic‐dependent individuals.     

Callosal thickness reductions relate to facial dysmorphology in fetal alcohol spectrum disorders

Background: Structural abnormalities of the corpus callosum (CC), such as reduced size and increased shape variability, have been documented in individuals with fetal alcohol spectrum disorders (FASD). However, the regional specificity of altered CC structure, which may point to the timing of neurodevelopmental disturbances and/or relate to specific functional impairments, remains unclear. Furthermore, associations between facial dysmorphology and callosal structure remain undetermined. Methods: One hundred and fifty‐three participants (age range 8 to 16) including 82 subjects with FASD and 71 nonexposed controls were included in this study. The structural magnetic resonance imaging data of these subjects was collected at 3 sites (Los Angeles and San Diego, California, and Cape Town, South Africa) and analyzed using classical parcellation schemes, as well as more refined surface‐based geometrical modeling methods, to identify callosal morphological alterations in FASD at high spatial resolution. Results: Reductions in callosal thickness and area, specifically in the anterior third and the splenium, were observed in FASD compared with nonexposed controls. In addition, reduced CC thickness and area significantly correlated with reduced palpebral fissure length. Conclusions: Consistent with previous reports, findings suggest an adverse effect of prenatal alcohol exposure on callosal growth and further indicate that fiber pathways connecting frontal and parieto‐occipital regions in each hemisphere may be particularly affected. Significant associations between callosal and facial dysmorphology provide evidence for a concurrent insult to midline facial and brain structural development in FASD.     

The Specific Gravity of the Brains of Alcoholic and Control Patients: a pathological study

In recent pathological studies the authors have shown that the brain shrinkage seen in alcoholics is due to a loss of tissue from the white matter and not the cortical grey matter. In order to address the question of the pathogenesis of this shrinkage the Specific Gravity (SG) of the frontal, parietal and occipital grey and white matter of alcoholics and age- and sex-matched controls was measured. The alcoholics were found to have a consistent, but not significant, reduction in SG. Alcoholics with Wernicke's encephalopathy (WE) showed similar changes. The decrease in SG in alcoholics with cirrhosis was significant. This pattern of change, in the absence of a large variation in brain water content, suggests that the loss of tissue is probably balanced so that protein/lipid/ carbohydrate ratios are not appreciably different in controls and alcoholics.     

In vivo detection and functional correlates of white matter microstructural disruption in chronic alcoholism

BACKGROUND: Postmortem studies report degradation of brain white matter microstructure in chronic alcoholism, but until recently, in vivo neuroimaging could provide measurement only at a macrostructural level. The development of magnetic resonance diffusion tensor imaging (DTI) for clinical use offers a method for depicting and quantifying the diffusion properties of white matter expressed as intravoxel and intervoxel coherence of tracts and fibers. METHODS: This study used DTI to examine the intravoxel coherence measured as fractional anisotropy (FA) and intervoxel coherence (C) of white matter tracts of the genu and splenium of the corpus callosum and of the centrum semiovale in 15 detoxified alcoholic men and 31 nonalcoholic control subjects. Exploratory correlational analyses examined the relationships between regional DTI measures and tests of attention and working memory in the alcoholic patients. RESULTS: The alcoholic group had lower regional FA than the control group. C was lower in the alcoholics than controls in the splenium only. Working memory correlated positively with splenium FA, whereas attention correlated positively with genu C. CONCLUSIONS: These results provide in vivo evidence for disruption of white matter microstructure in alcoholism and suggest that interruption of white matter fiber coherence contributes to disturbance in attention and working memory in chronic alcoholism.     

Effects of Chronic Alcohol Abuse and HIV Infection on Brain Phosphorus Metabolites

We examined the effects of human immunodeficiency virus (HIV) infection and chronic alcohol consumption on cerebral phosphorus metabolites to determine if chronic alcohol abuse is a risk factor for the progression of neurological effects of HIV infection. We studied 15 HIV- alcoholics, 8 HIV- light/nondrinkers, 32 HIV+ alcoholics, and 41 HIV+ light/nondrinking men, with both HIV+ groups having similar CD4 lymphocyte counts. We used localized 31-phosphorus magnetic resonance spectroscopy after magnetic resonance imaging to examine two brain volumes in superior white matter and subcortical gray matter. Chronic alcohol consumption was associated with reduced white matter concentrations of phosphodiester (PDE) and phosphocreatine (PCr). Also in the white matter, acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) were associated with reduced concentrations of PDE and PCr, compared with both HIV- and clinically asymptomatic HIV+ subjects. Because no alcohol-by-HIV interactions were detected, the effects of HIV infection and alcohol abuse were cumulative. This is reflected in a successive decrease of white matter PDE and PCr concentrations in the order HIV- light/nondrinkers/HIV- alcoholics/HIV+ light/nondrinkers/HIV+ alcoholics. Subcortical gray matter PDE concentrations were lower in ARC/AIDS alcoholics than in HIV-light/nondrinking individuals. These findings suggest altered brain phospholipid metabolites and energy metabolites with alcohol abuse and HIV infection. They demonstrate that the adverse metabolic effects of HIV on the brain are augmented by chronic alcohol abuse.     

Frontal Lobe Volume Loss Observed with Magnetic Resonance Imaging in Older Chronic Alcoholics

This study used magnetic resonance imaging to quantify the extent and pattern of tissue volume deficit and cerebrospinal fluid volume enlargement in younger versus older chronic alcoholics relative to normal controls. In the present analysis, we divided our previously reported group of 62 alcoholic men into a younger group (n = 33, age mean = 37.5 ± 4.5, and range = 26 to 44 years) and an older group ( n = 29, age mean = 52.7 ± 6.0, and range = 45 to 63 years) to examine whether, in addition to extent, the two age groups differed in pattern of tissue type and regional brain volume abnormalities quantified with magnetic resonance imaging. Brain volumes were adjusted for normal variation in head size and age established from a group of healthy controls and were expressed as Z-scores. The younger group had significant cortical gray, but not white, matter volume deficits and sulcal and ventricular enlargement relative to age-matched controls. The older group had volume deficits in both cortical gray and white matter and sulcal and ventricular enlargement that significantly exceeded the younger alcoholic group. An analysis of six cortical regions revealed that, although both age groups had gray matter volume deficits throughout the cortex, the older alcoholic group had a selectively more severe deficit in prefrontal gray matter relative to the younger alcoholic group. Similarly, the cortical white matter volume deficit in the older alcoholics was especially severe in the prefrontal and frontal regions. The differences in brain dysmorphology between the two alcoholic groups cannot easily be attributed to potential alcohol history differences typically related to age because the two groups had similar disease durations and amounts of lifetime alcohol consumption. These results provide in vivo evidence that the frontal lobes are especially vulnerable to chronic alcoholism in older men.     

Altered White Matter Integrity in Adolescent Binge Drinkers

Background:  White matter integrity has been found to be compromised in adult alcoholics, but it is unclear when in the course of alcohol exposure white matter abnormalities become apparent. This study assessed microstructural white matter integrity among adolescent binge drinkers with no history of an alcohol use disorder.
Methods:  We used diffusion tensor imaging to examine fractional anisotropy (FA), a measure of directional coherence of white matter tracts, among teens with ( n  =   14) and without ( n  =   14) histories of binge drinking but no history of alcohol use disorder, matched on age, gender, and education.
Results:  Binge drinkers had lower FA than controls in 18 white matter areas (clusters ≥27 contiguous voxels, each with p  < 0.01) throughout the brain, including the corpus callosum, superior longitudinal fasciculus, corona radiata, internal and external capsules, and commissural, limbic, brainstem, and cortical projection fibers, while exhibiting no areas of higher FA. Among binge drinkers, lower FA in 6 of these regions was linked to significantly greater lifetime hangover symptoms and/or higher estimated peak blood alcohol concentrations.
Conclusions:  Binge drinking adolescents demonstrated widespread reductions of FA in major white matter pathways. Although preliminary, these results could indicate that infrequent exposure to large doses of alcohol during youth may compromise white matter fiber coherence.     

Anterior Hippocampal Volume Deficits in Nonamnesic, Aging Chronic Alcoholics

Magnetic resonance imaging was used to quantify the volume of the hippocampus in 47 men with chronic alcoholism and 72 healthy male control subjects. The subjects ranged in age from 21 to 70 years, thus permitting a test of whether older alcoholics suffer greater brain tissue volume reduction than do younger ones. Comparison brain regions included temporal lobe gray matter, white matter, and cerebrospinal fluid, as well as measures of the lateral ventricles, third ventricle, and temporal horns. The results of this cross-sectional study showed that the anterior, but not the posterior, portions of the hippocampus in both hemispheres were significantly smaller in the alcoholic than the healthy control group. Furthermore, the bilateral anterior hippocampal volume loss was greater in older than younger alcoholics. Despite the hippocampal volume deficit, these alcoholics did not demonstrate an explicit memory impairment; furthermore, memory test scores did not correlate significantly with hippocampal volumes. In the alcoholics, the age-related volume loss, which was over and above that expected in normal aging, was also evident in the temporal cortex and white matter. Likewise, alcoholic ventricular enlargement was age-related. Analysis of covariance revealed that the anterior hippocampal deficit persisted after accounting for the temporal lobe gray matter volume deficit. Multiple regression analysis revealed that the age-related brain volume abnormalities observed in the alcoholics could not be attributed to duration of alcoholism or total lifetime consumption of alcohol.     

Inter-hemispheric functional connectivity disruption in children with prenatal alcohol exposure

Background: MRI studies, including recent diffusion tensor imaging (DTI) studies, have shown corpus callosum abnormalities in children prenatally exposed to alcohol, especially in the posterior regions. These abnormalities appear across the range of fetal alcohol spectrum disorders (FASD). Several studies have demonstrated cognitive correlates of callosal abnormalities in FASD including deficits in visual‐motor skill, verbal learning, and executive functioning. The goal of this study was to determine whether inter‐hemispheric structural connectivity abnormalities in FASD are associated with disrupted inter‐hemispheric functional connectivity and disrupted cognition. Methods: Twenty‐one children with FASD and 23 matched controls underwent a 6‐minute resting‐state functional MRI scan as well as anatomical imaging and DTI. Using a semi‐automated method, we parsed the corpus callosum and delineated 7 inter‐hemispheric white matter tracts with DTI tractography. Cortical regions of interest (ROIs) at the distal ends of these tracts were identified. Right–left correlations in resting fMRI signal were computed for these sets of ROIs, and group comparisons were made. Correlations with facial dysmorphology, cognition, and DTI measures were computed. Results: A significant group difference in inter‐hemispheric functional connectivity was seen in a posterior set of ROIs, the para‐central region. Children with FASD had functional connectivity that was 12% lower than in controls in this region. Subgroup analyses were not possible owing to small sample size, but the data suggest that there were effects across the FASD spectrum. No significant association with facial dysmorphology was found. Para‐central functional connectivity was significantly correlated with DTI mean diffusivity, a measure of microstructural integrity, in posterior callosal tracts in controls but not in FASD. Significant correlations were seen between these structural and functional measures, and Wechsler perceptual reasoning ability. Conclusions: Inter‐hemispheric functional connectivity disturbances were observed in children with FASD relative to controls. The disruption was measured in medial parietal regions (para‐central) that are connected by posterior callosal fiber projections. We have previously shown microstructural abnormalities in these same posterior callosal regions, and the current study suggests a possible relationship between the two. These measures have clinical relevance as they are associated with cognitive functioning.     

Effects of abstinence from alcohol on the broad phospholipid signal in human brain: an in vivo 31P magnetic resonance spectroscopy study

BACKGROUND: In vivo phosphorus magnetic resonance spectroscopy (31P MRS) at a magnetic field strength of 1.5 T allows measurement of fairly mobile membrane phospholipids in the human brain. We previously showed that subjects who are heavy drinkers had a smaller signal and a shorter transverse relaxation time (T2) of white matter phospholipids than light drinkers, which suggested lower concentrations and molecular mobility of phospholipids in heavy drinkers. The purpose of the present study was to measure if such chronic alcohol-induced white matter tissue changes are persistent in long-term abstinent alcoholics. METHODS: Fourteen abstinent alcoholics (mean age 45 years, seven men and seven women) were studied by localized 31P MRS in the centrum semiovale and were compared with 13 male, alcohol-dependent, heavy drinkers and 23 nondependent light drinkers (17 men, 6 women) of similar age. Methods for measurements of the broad membrane phospholipid signal and its relaxation time were described previously. RESULTS: Phospholipid concentrations and relaxation times in alcoholics abstinent for an average of 31 months were not significantly different from those measured in light drinkers. The contribution of fast and slowly relaxing signal components to the broad phospholipid signal, however, was still different in abstinent alcoholics compared with light drinkers. No effects of sex or of family history of alcoholism were noted on any of our spectroscopic measures within the light-drinking or abstinent groups. CONCLUSIONS: Most of our results suggest at least partial recovery of chronic alcohol-induced white matter phospholipid damage with long-term abstinence. They offer myelination changes and/or dendritic rearborization as a possible mechanism for the commonly observed white matter volume gain with prolonged abstinence. But the results also suggest a persistent abnormality in the nature and/or physical properties of white matter phospholipids in long-term abstinent alcoholics.     

Improvement of left ventricular function in chronic alcoholics following abstinence from ethanol

Preclinical abnormalities of left ventricular function are frequently found in chronic alcoholics. In 12 chronic alcoholics without cardiomyopathy and in 12 healthy controls, systolic time intervals and echocardiograms were investigated before and after 12 months of abstinence from alcohol. In chronic alcoholics, an increase was found in the PEP/LVET ratio (0.31 +/- 0.06; in controls 0.24 +/- 0.05; t = 3.11; p less than 0.005), the diastolic interventricular septal thickness (6.0 +/- 2.0 mm/m2; in controls 4.1 +/- 1.0; t = 2.95; p less than 0.01), the left ventricular wall thickness (6.3 +/- 1.0 mm/m2; in controls 4.9 +/- 1.0; t = 3.43; p less than 0.005) and the left ventricular diastolic dimension (29 +/- 4 mm/m2; in controls 26 +/- 3; t = 2.08; p less than 0.05). The left ventricular mass (135 +/- 33 g/m2; in controls 113 +/- 40; t = 1.47) did not differ from the controls. After 12 months of abstinence a significant decrease was found in the PEP/LVET ratio (0.26 +/- 0.05, i.e. -16%; t = 3.59; p less than 0.005), the diastolic interventricular septal thickness (4.7 +/- 0.9 mm/m2, i.e. -22%; t = 2.73; p less than 0.02), the left ventricular posterior wall thickness (5.6 +/- 1.0 mm/m2, i.e. -11%; t = 4.08; p less than 0.001) and the left ventricular mass (109 +/- 24 g/m2, i.e. -21%; t = 6.53; p less than 0.001). The left ventricular diastolic dimension (27 +/- 2 mm/m2, i.e. -7%; t = 1.3) did not change. In conclusion, in chronic alcoholics, the abstinence from alcohol can be followed by an improvement of left ventricular function.     

Chemical Pathology in Brain White Matter of Recently Detoxified Alcoholics: A 1H Magnetic Resonance Spectroscopy Investigation of Alcohol-Associated Frontal Lobe Injury

BACKGROUND: Investigations have suggested that frontal lobe abnormalities are a prominent feature of the alcoholic brain, indicated by impaired neuropsychological performance on tests of frontal lobe function and by reduced frontal lobe volume in neuroimaging and neuropathological examinations. White matter compartment volume loss may underlie observed brain shrinkage and cognitive deficits associated with the frontal lobes, although the nature of this change has not been well-characterized. METHOD: To investigate the susceptibility of frontal lobe white matter to alcohol-associated metabolic change and to understand the nature of alcohol-related white matter injury, 1H magnetic resonance spectroscopy (MRS) was used 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), choline-containing compounds (Cho), myo-inositol (Ins), and creatine plus phosphocreatine (Cr) were measured in 37 RDA (mean age, 40.4 years; mean length of abstinence, 27.9 days) and 15 CON (mean age, 38.0 years). RESULTS: Analysis of variance (ANOVA) revealed a group by region of interest interaction for concentrations of NAA. Simple effects analysis revealed a significant 14.7% reduction in FWM NAA, while NAA levels in PWM were similar 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. Reductions in FWM NAA were associated with a longer drinking history in the RDA group, 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-induced oxidative stress may cause global brain impairments in the metabolism and subsequent reduction of NAA, the frontal lobes are particularly rich in excitatory amino acid pathways, and axonal damage or destruction secondary to glutamate-mediated excitotoxicity during alcohol withdrawal may cause frontal lobe-specific reductions in NAA. Elevations in brain white matter Ins may reflect astrocyte proliferation as well as an osmotic response to cell shrinkage.