Alcohol. Vol. 8, p~'. 31-34. ~ Pergamon Press plc. 1991. Printed in the U.S.A.
0741-8329/91 $3.00 + .00
Brain Ventricular Size in Female Alcoholics: An MRI Study C A R A L E R N E R K R O F T , B R Y A N G E S C U K , B R Y A N T. W O O D S , * N A N C Y K. M E L L O , R O G E R D. W E I S S t A N D J A C K H. M E N D E L S O N l
*Alcohol and Drug Abuse Research Center, Neurology Department ?Alcohol and Drug Abuse Treatment Center McLean Hospital-Harvard Medical School, Belmont, MA 02178 R e c e i v e d 12 April 1990; A c c e p t e d 6 A u g u s t 1990
KROFT, C. L., B. GESCUK, B. T. WOODS, N. K. MELLO, R. D. WEISS AND J. H. MENDELSON. Brain ventricularsize in female alcoholics: An MRI study. ALCOHOL 8(1) 31-34, 1991.--The brains of ten alcohol-dependent women between the ages of 21 and 65 were studied with Magnetic Resonance Imaging (MR/) techniques. All women had MRI scans twice during the withdrawal period. Only one of the ten women had abnormally enlarged ventricles. At the time of the second scan there were no significant changes in ~ventricularsize from the first scan. No correlations were found between age and ventricular size, or years of alcohol abuse and ventricular size. Alcohol-dependent women
Magnetic Resonance Imaging
Brain ventricle size
A number of investigators have reported cerebral atrophy and ventricular dilatation in men with histories of alcohol abuse and dependence (6, 12, 13). Necropsy record analyses revealed that the mean fresh brain weight of 168 male alcoholics was significantly less than that of a normal population (6). Similarly, pathological specimens from 20 male alcoholics indicated that the alcoholics' mean brain weight was significantly lower than that of controls (12). Other investigators found that 22 chronic alcoholics showed a' significant loss of brain tissue when compared to controls (6). The tissue loss was primarily white matter in the brain (6). Radiologic studies have been carded out for sequential examination of changes in alcoholics' brains through time. Magnetic Resonance Imaging (MRI) techniques were used to scan the brains of ten chronic male alcoholics within two weeks of withdrawal and again one month later (13). Initially, the alcoholics' lateral ventricles were found to be significantly larger than controls'. However one month later, the ventricles of the alcoholic patients had decreased in size and were no longer significantly larger than controls'. The size of control subjects' ventricles remained constant during this period of observation. Reversibility of ventricular enlargement combined with white matter tissue loss suggests that alcohol-induced atrophy may be due to a decrease in white matter or a change in hydration. Alterations in ventricular size observed in chronic male alcoholics have not been found in female alcoholics (2, 5, 12). For example, male alcoholics had smaller brain weights at necropsy than normal males, but female alcoholics did have significant re-
duction in normal brain weight (7,12). However, the number of female alcoholics studied to date has been quite small ( N = 5 ) (12). Computerized Tomography (CT) scan studies also revealed that the degree of cerebral atrophy was always greater in male alcoholics than in female alcoholics (1). It also has been found in studies with normal subjects, that brains of males and females appear to atrophy differently during aging; men show more frontal lobe atrophy than women of comparable ages (2). Magnetic Resonance Imaging (MRI) techniques may be used to selectively examine cerebrospinal fluid (CS) compartments and may therefore he more sensitive to measures of changes in ventricular volumes than other radiological techniques. We are not aware of any MRI studies which have examined female alcoholics' brains sequentially during a period of alcohol abstinence. Our study, employing Magnetic Resonance Imaging, was designed to answer the following questions: I) Do female alcoholics' cerebral ventricles change in size during the course of abstinence and, if so, in what direction? 2) How do these changes compare with findings reported for male alcoholics? and 3) Are there any differences in the sizes of alcoholic women's ventricles in comparison to those of normal women? PROCEDURES
Subjects Ten women between the ages of 21 and 65 were recruited from the Massachusetts Osteopathic Hospital where they had been
'Requests for reprintsshould be addressed to Jack H. Mendelson, M.D., McLean Hospital, 115 Mill Sa'eet, Belmont, M A 02178.
31
32
KROFT ET AL.
TABLE I DEMOGRAPHICS
Subject No.
Age
Years Education
Ethanol Abuse (Years)
g/kg/day Last Month
g/kg/day Last Year
Race
1 2 3 4 5 6 7 8 9 10
61 38 28 25 28 22 27 35 51 22
16 12 14 10 13 10 12 14 8 12
40 4 6 7 16 5 10 12 22 4
2.96 1.23 66.87 5.14 3.13 4.82 6.38 6.38 6.59 2.21
2.96 0.82 6.87 2.21 3.13 4.82 6.38 4.79 6.59 2.21
Caucasian Black Hispanic Caucasian Black Caucasian Caucasian Caucasian Caucasian Caucasian
remanded for treatment of substance abuse. All subjects met DSM-III-R criteria for alcohol dependence. Exclusion criteria included significant liver function abnormalities, known central nervous system abnormalities, significant use of illicit drugs other thaa alcohol and use of central nervous system medication other than those used during the detoxification period. Informed consent was obtained from each subject and the women were paid fifty dollars for their participation in the study. Patients were escorted by one of the investigators to McLean Hospital where they received their first MRI scan as soon as possible after admission. The second MRI scan was carried out prior to each patient's discharge from Massachusetts Osteopathic Hospital in order to maximize the time interval of alcohol abstinence between the first and second scans. METHOD
All scans were carried out with a G.E. 1.5 Tesla Signa system with Tl-weighted spin-echo sequences (TR = 500; TE = 20). Ventricular size was measured using a modification of the technique described by Pfefferbaum et at. (10) for CT, in which the same image was displayed on a split screen, windowed normally on one side and with a 0-1 range on the other side. The level control for the black-white image was then varied until the silhou-
ette of the structure of interest appeared to match the size and shape of the same structure on the gray-scale image. The intensity level giving the best match then determined the boundary of the structure. Since image intensity may vary from slice to slice, the boundary threshold is found separately for each slice. Once this threshold was determined, all pixels of higher intensity were hulled, and the remaining structure was then traced and measured using a console cursor. The brain border was then traced separately on the full-range image and brain area calculated by the system software. RESULTS As shown in Table 1, the subjects varied in age, years of ethanol abuse, amount of ethanol consumed and the timing of their scans. They also differed from one another in terms of absolute ventricular volumes (see Table 2) although all but Subject number 3 were within the norm for women of a similar age group studied by Skullerud and colleagues (mean lateral ventricular volume for women aged 45 to 54 years was 17.6---4.9 ml) (12). No subject exhibited a significant change in ventricular size from scan 1 to scan 2 (see Fig. 1). There were also no significant correlations found between size of ventricles and age, r 2 = . 2 4 6 , p = 0 . 1 4 5 , or size of ventricles
TABLE 2 VENTRICULAR (V) SIZE IN ALCOHOLIC WOMEN
Subject No.
V (cc) 1
V (cc) 2
I 2 3 4 5 6 7 8 9 10 Mean =
23.89 17.83 31.71 8.80 5.42 9.50 12.10 11.45 19.20 11.01 15.09
20.87 18.86 30.50 9.18 5.78 9.27 11.99 10.17 20.67 11.79 14.91
*L.D. = last drink prior to MR/.
*L.D.-lst MRI (Days)
2nd MR/ Scan-Scan (Days)
10 22 46 51 16 3 19 19 160 30
67 38 28 27 26 33 90 52 38 35
FEMALE ALCOHOLICS
401
Ventricular
33
Change
in S i z e b y S c a n
30
.~
m
Scan
1
~
Scan
2
20
lO
o
61
51
38
35
28
28
27
25
22
22
SubJecls' Ages (years) PsIred I-Teet XI: scan 1
YI: scan2
DF.
Mear~X - Y
Parred I value;
Prob. 12-lad~:
I,
1,8
1,3
168
I
FIG. 1. Ventricular size at first and second scan after cessation of drinking.
and years of alcohol abuse, r2 = .084, p = 0 . 4 1 5 8 . However, when the calculations were carried out excluding Subject number 3, whose ventricles were abnormally large, the correlation between ventricular size and age was highly significant, r 2 = . 8 0 1 , p = 0.0011. Thus the lack of a significant correlation between age and ventricular size may reflect the compounding effect of one subject in a small population. DISCUSSION The findings obtained in this study indicate that female alcoholics do not have changes in ventricular size that have been found in male alcoholics (Table 2). The average ventricular volume of the female alcoholics in this study was within the normal range of ventricular volumes found in studies of nonalcoholic women of a similar age range (12). This contrasts with previous reports that alcoholic men show significant ventricular dilatation when compared to age-matched normals (6, 12, 13). Our findings are consistent with the pathological and radiological findings of other investigators (5,12). However, it is important to note that all of these studies, in-
cluding our own, have consisted of a relatively small number of subjects. One possible explanation for the lack of ventricular dilatation in our study is that the average age of our subjects was quite young (33.7 years). Some investigators have found that young male alcoholics may exhibit sulcal widening but do not have ventricular dilatation (9). However, even our subjects over the age of 50 did not exhibit a significant change in ventricular volume from their flu'st scan to their second. Many studies have shown that the ventricular dilatation noted in male alcoholics is reversible after a variable period of abstinence (3, 11, 13). Our study showed no significant change in women's ventricular volumes from the first to the second scan (Fig. 1). Absence of change would be expected if, as our findings suggest, there was no ventricular dilatation found on the first MRI scan. It is possible that the subjects' ventricles may have been dilated and then diminished in size prior to their first MRI scan. However, subjects who were studied within ten days of their last drink showed no significant change in ventricular size from their first to their second scan. In summary, this study found that female alcoholics may not exhibit the significant ventricular dilatation similar to that found in male alcoholics and that the cerebral changes which occur during abstinence may differ between the two groups. Male and female alcoholics may have a number of clinically important difficulties. For example, it has been reported that women may be more vulnerable to the biomedical consequences of alcoholism (4,8). In the light of these differences, caution should be exercised in making assumptions about the treatment of female alcoholics on the basis of studies carried out with males. Our findings highlight the need for further research with female alcoholics in order to elucidate gender-related factors which may effect treatment and prognosis for recovery. NOTE ADDED IN PROOF
Since submission and acceptance of this report, Andreasen and her colleagues have found significant gender-related differences in brain ventricular size in patients with a diagnosis of schizophrenia. Andreasen, N. C.; Swayze, V. W.; Flaum, M.; Yates, W. R.; Amdt, S.; McChesney, C. Ventricular enlargement in schizophrenia evaluated with computed tomographic scanning. Arch. Gen. Psychiatry 47:1008-1015; 1990. ACKNOWLEDGEMENTS This study was supported in part by grant AA06252 from the National Institute on Alcohol Abuse and Alcoholism, and grants DA00064 and DA00101 from the National Institute on Drug Abuse.
REFERENCES 1. Cala, L.; Mastaglia, F. Computerized Axial Tomography in the detection of brain damage. Med. J. Aust. 2:193-198; 1980. 2. Cala, L. A.; Thickbroom, G. W.; Black, J. L.; Collins, D. W.; Mastaglia, F. L. Brain density and cerebrospinal fluid spaces on the cranial CT scan in normal volunteers. Am. J. Neuroradiol. 2:41-47; 1981. 3. Carlen, P. L.; Wortzman, G.; Holgate, R. C.; Wilkinson, D. A.; Rankin, J. G. Reversible cerebral atrophy in recently abstinent chronic alcoholics measured by computed tomographic scans. Science 200: 1076-1078; 1978. 4. Dahlgren, M.; ldestrom, C. M. Female alcoholics v. morbidity. Acta Psychiatr. Scand. 60:199-213; 1979. 5. Harper, C. G.; Blumbergs, P. C. Brain weight in alcoholics. J. Neurol. Neurosurg. Psychiatry 45:838-840; 1982.
6. Harper, C. G.; Kill, J. J.; Holloway, R. L. Brain shrinkage in chronic alcoholics: A pathological study. Br. Med. J. 290:501-504; 1985. 7. Lishman, W. A.; Jacobson, R. R.; Acker, C. Brain damage in alcoholism: Current concepts. Acta Med. Scand. 222(Suppl.)717:5-17; 1987. 8. Medhus, A. Morbidity among female alcoholics. Scand. J. Soc. Med. 2:5-11; 1974. 9. Pfefferbaum, A.; Rosenbloom, M.; Crusan, K.; Jernigan, T. Brain CT changes in alcoholics: Effects of age and alcohol consumption. Alcohol.: Clin. Exp. Res. 12:81-86; 1988. 10. Pfefferbanm, A.; Zatz, L. M.; Jemigan, T. L. Computer-interactive method for quantifying cerebral spinal fluid and tissue in brain CT scans: Effects of aging. J. Comput. Assist. Tomogr. 10:571-578; 1986.
34
11. Schroth, G.; Nacgele, T.; Klose, U.; Mann, K.; Petersen, D. Reversible brain shrinkage in abstinent alcoholics measured by MRI. Neuroradiology 30:385-389; 1988. 12. SkuUerud, K. Variations in the size of the human brain. Acta Neu-
KROFI" ET AL.
rol. Scand. Suppl. 102:1-112; 1985. 13. Zipursky, R. B.; Lim K. O.; Pfefferbaum, A. MRI study of brain changes with short-term abstinence from alcohol. Alcohol.: Clin. Exp. Res. 13:664-666; 1989.
0741-8329/91 $3.00 + .00
Brain Ventricular Size in Female Alcoholics: An MRI Study C A R A L E R N E R K R O F T , B R Y A N G E S C U K , B R Y A N T. W O O D S , * N A N C Y K. M E L L O , R O G E R D. W E I S S t A N D J A C K H. M E N D E L S O N l
*Alcohol and Drug Abuse Research Center, Neurology Department ?Alcohol and Drug Abuse Treatment Center McLean Hospital-Harvard Medical School, Belmont, MA 02178 R e c e i v e d 12 April 1990; A c c e p t e d 6 A u g u s t 1990
KROFT, C. L., B. GESCUK, B. T. WOODS, N. K. MELLO, R. D. WEISS AND J. H. MENDELSON. Brain ventricularsize in female alcoholics: An MRI study. ALCOHOL 8(1) 31-34, 1991.--The brains of ten alcohol-dependent women between the ages of 21 and 65 were studied with Magnetic Resonance Imaging (MR/) techniques. All women had MRI scans twice during the withdrawal period. Only one of the ten women had abnormally enlarged ventricles. At the time of the second scan there were no significant changes in ~ventricularsize from the first scan. No correlations were found between age and ventricular size, or years of alcohol abuse and ventricular size. Alcohol-dependent women
Magnetic Resonance Imaging
Brain ventricle size
A number of investigators have reported cerebral atrophy and ventricular dilatation in men with histories of alcohol abuse and dependence (6, 12, 13). Necropsy record analyses revealed that the mean fresh brain weight of 168 male alcoholics was significantly less than that of a normal population (6). Similarly, pathological specimens from 20 male alcoholics indicated that the alcoholics' mean brain weight was significantly lower than that of controls (12). Other investigators found that 22 chronic alcoholics showed a' significant loss of brain tissue when compared to controls (6). The tissue loss was primarily white matter in the brain (6). Radiologic studies have been carded out for sequential examination of changes in alcoholics' brains through time. Magnetic Resonance Imaging (MRI) techniques were used to scan the brains of ten chronic male alcoholics within two weeks of withdrawal and again one month later (13). Initially, the alcoholics' lateral ventricles were found to be significantly larger than controls'. However one month later, the ventricles of the alcoholic patients had decreased in size and were no longer significantly larger than controls'. The size of control subjects' ventricles remained constant during this period of observation. Reversibility of ventricular enlargement combined with white matter tissue loss suggests that alcohol-induced atrophy may be due to a decrease in white matter or a change in hydration. Alterations in ventricular size observed in chronic male alcoholics have not been found in female alcoholics (2, 5, 12). For example, male alcoholics had smaller brain weights at necropsy than normal males, but female alcoholics did have significant re-
duction in normal brain weight (7,12). However, the number of female alcoholics studied to date has been quite small ( N = 5 ) (12). Computerized Tomography (CT) scan studies also revealed that the degree of cerebral atrophy was always greater in male alcoholics than in female alcoholics (1). It also has been found in studies with normal subjects, that brains of males and females appear to atrophy differently during aging; men show more frontal lobe atrophy than women of comparable ages (2). Magnetic Resonance Imaging (MRI) techniques may be used to selectively examine cerebrospinal fluid (CS) compartments and may therefore he more sensitive to measures of changes in ventricular volumes than other radiological techniques. We are not aware of any MRI studies which have examined female alcoholics' brains sequentially during a period of alcohol abstinence. Our study, employing Magnetic Resonance Imaging, was designed to answer the following questions: I) Do female alcoholics' cerebral ventricles change in size during the course of abstinence and, if so, in what direction? 2) How do these changes compare with findings reported for male alcoholics? and 3) Are there any differences in the sizes of alcoholic women's ventricles in comparison to those of normal women? PROCEDURES
Subjects Ten women between the ages of 21 and 65 were recruited from the Massachusetts Osteopathic Hospital where they had been
'Requests for reprintsshould be addressed to Jack H. Mendelson, M.D., McLean Hospital, 115 Mill Sa'eet, Belmont, M A 02178.
31
32
KROFT ET AL.
TABLE I DEMOGRAPHICS
Subject No.
Age
Years Education
Ethanol Abuse (Years)
g/kg/day Last Month
g/kg/day Last Year
Race
1 2 3 4 5 6 7 8 9 10
61 38 28 25 28 22 27 35 51 22
16 12 14 10 13 10 12 14 8 12
40 4 6 7 16 5 10 12 22 4
2.96 1.23 66.87 5.14 3.13 4.82 6.38 6.38 6.59 2.21
2.96 0.82 6.87 2.21 3.13 4.82 6.38 4.79 6.59 2.21
Caucasian Black Hispanic Caucasian Black Caucasian Caucasian Caucasian Caucasian Caucasian
remanded for treatment of substance abuse. All subjects met DSM-III-R criteria for alcohol dependence. Exclusion criteria included significant liver function abnormalities, known central nervous system abnormalities, significant use of illicit drugs other thaa alcohol and use of central nervous system medication other than those used during the detoxification period. Informed consent was obtained from each subject and the women were paid fifty dollars for their participation in the study. Patients were escorted by one of the investigators to McLean Hospital where they received their first MRI scan as soon as possible after admission. The second MRI scan was carried out prior to each patient's discharge from Massachusetts Osteopathic Hospital in order to maximize the time interval of alcohol abstinence between the first and second scans. METHOD
All scans were carried out with a G.E. 1.5 Tesla Signa system with Tl-weighted spin-echo sequences (TR = 500; TE = 20). Ventricular size was measured using a modification of the technique described by Pfefferbaum et at. (10) for CT, in which the same image was displayed on a split screen, windowed normally on one side and with a 0-1 range on the other side. The level control for the black-white image was then varied until the silhou-
ette of the structure of interest appeared to match the size and shape of the same structure on the gray-scale image. The intensity level giving the best match then determined the boundary of the structure. Since image intensity may vary from slice to slice, the boundary threshold is found separately for each slice. Once this threshold was determined, all pixels of higher intensity were hulled, and the remaining structure was then traced and measured using a console cursor. The brain border was then traced separately on the full-range image and brain area calculated by the system software. RESULTS As shown in Table 1, the subjects varied in age, years of ethanol abuse, amount of ethanol consumed and the timing of their scans. They also differed from one another in terms of absolute ventricular volumes (see Table 2) although all but Subject number 3 were within the norm for women of a similar age group studied by Skullerud and colleagues (mean lateral ventricular volume for women aged 45 to 54 years was 17.6---4.9 ml) (12). No subject exhibited a significant change in ventricular size from scan 1 to scan 2 (see Fig. 1). There were also no significant correlations found between size of ventricles and age, r 2 = . 2 4 6 , p = 0 . 1 4 5 , or size of ventricles
TABLE 2 VENTRICULAR (V) SIZE IN ALCOHOLIC WOMEN
Subject No.
V (cc) 1
V (cc) 2
I 2 3 4 5 6 7 8 9 10 Mean =
23.89 17.83 31.71 8.80 5.42 9.50 12.10 11.45 19.20 11.01 15.09
20.87 18.86 30.50 9.18 5.78 9.27 11.99 10.17 20.67 11.79 14.91
*L.D. = last drink prior to MR/.
*L.D.-lst MRI (Days)
2nd MR/ Scan-Scan (Days)
10 22 46 51 16 3 19 19 160 30
67 38 28 27 26 33 90 52 38 35
FEMALE ALCOHOLICS
401
Ventricular
33
Change
in S i z e b y S c a n
30
.~
m
Scan
1
~
Scan
2
20
lO
o
61
51
38
35
28
28
27
25
22
22
SubJecls' Ages (years) PsIred I-Teet XI: scan 1
YI: scan2
DF.
Mear~X - Y
Parred I value;
Prob. 12-lad~:
I,
1,8
1,3
168
I
FIG. 1. Ventricular size at first and second scan after cessation of drinking.
and years of alcohol abuse, r2 = .084, p = 0 . 4 1 5 8 . However, when the calculations were carried out excluding Subject number 3, whose ventricles were abnormally large, the correlation between ventricular size and age was highly significant, r 2 = . 8 0 1 , p = 0.0011. Thus the lack of a significant correlation between age and ventricular size may reflect the compounding effect of one subject in a small population. DISCUSSION The findings obtained in this study indicate that female alcoholics do not have changes in ventricular size that have been found in male alcoholics (Table 2). The average ventricular volume of the female alcoholics in this study was within the normal range of ventricular volumes found in studies of nonalcoholic women of a similar age range (12). This contrasts with previous reports that alcoholic men show significant ventricular dilatation when compared to age-matched normals (6, 12, 13). Our findings are consistent with the pathological and radiological findings of other investigators (5,12). However, it is important to note that all of these studies, in-
cluding our own, have consisted of a relatively small number of subjects. One possible explanation for the lack of ventricular dilatation in our study is that the average age of our subjects was quite young (33.7 years). Some investigators have found that young male alcoholics may exhibit sulcal widening but do not have ventricular dilatation (9). However, even our subjects over the age of 50 did not exhibit a significant change in ventricular volume from their flu'st scan to their second. Many studies have shown that the ventricular dilatation noted in male alcoholics is reversible after a variable period of abstinence (3, 11, 13). Our study showed no significant change in women's ventricular volumes from the first to the second scan (Fig. 1). Absence of change would be expected if, as our findings suggest, there was no ventricular dilatation found on the first MRI scan. It is possible that the subjects' ventricles may have been dilated and then diminished in size prior to their first MRI scan. However, subjects who were studied within ten days of their last drink showed no significant change in ventricular size from their first to their second scan. In summary, this study found that female alcoholics may not exhibit the significant ventricular dilatation similar to that found in male alcoholics and that the cerebral changes which occur during abstinence may differ between the two groups. Male and female alcoholics may have a number of clinically important difficulties. For example, it has been reported that women may be more vulnerable to the biomedical consequences of alcoholism (4,8). In the light of these differences, caution should be exercised in making assumptions about the treatment of female alcoholics on the basis of studies carried out with males. Our findings highlight the need for further research with female alcoholics in order to elucidate gender-related factors which may effect treatment and prognosis for recovery. NOTE ADDED IN PROOF
Since submission and acceptance of this report, Andreasen and her colleagues have found significant gender-related differences in brain ventricular size in patients with a diagnosis of schizophrenia. Andreasen, N. C.; Swayze, V. W.; Flaum, M.; Yates, W. R.; Amdt, S.; McChesney, C. Ventricular enlargement in schizophrenia evaluated with computed tomographic scanning. Arch. Gen. Psychiatry 47:1008-1015; 1990. ACKNOWLEDGEMENTS This study was supported in part by grant AA06252 from the National Institute on Alcohol Abuse and Alcoholism, and grants DA00064 and DA00101 from the National Institute on Drug Abuse.
REFERENCES 1. Cala, L.; Mastaglia, F. Computerized Axial Tomography in the detection of brain damage. Med. J. Aust. 2:193-198; 1980. 2. Cala, L. A.; Thickbroom, G. W.; Black, J. L.; Collins, D. W.; Mastaglia, F. L. Brain density and cerebrospinal fluid spaces on the cranial CT scan in normal volunteers. Am. J. Neuroradiol. 2:41-47; 1981. 3. Carlen, P. L.; Wortzman, G.; Holgate, R. C.; Wilkinson, D. A.; Rankin, J. G. Reversible cerebral atrophy in recently abstinent chronic alcoholics measured by computed tomographic scans. Science 200: 1076-1078; 1978. 4. Dahlgren, M.; ldestrom, C. M. Female alcoholics v. morbidity. Acta Psychiatr. Scand. 60:199-213; 1979. 5. Harper, C. G.; Blumbergs, P. C. Brain weight in alcoholics. J. Neurol. Neurosurg. Psychiatry 45:838-840; 1982.
6. Harper, C. G.; Kill, J. J.; Holloway, R. L. Brain shrinkage in chronic alcoholics: A pathological study. Br. Med. J. 290:501-504; 1985. 7. Lishman, W. A.; Jacobson, R. R.; Acker, C. Brain damage in alcoholism: Current concepts. Acta Med. Scand. 222(Suppl.)717:5-17; 1987. 8. Medhus, A. Morbidity among female alcoholics. Scand. J. Soc. Med. 2:5-11; 1974. 9. Pfefferbaum, A.; Rosenbloom, M.; Crusan, K.; Jernigan, T. Brain CT changes in alcoholics: Effects of age and alcohol consumption. Alcohol.: Clin. Exp. Res. 12:81-86; 1988. 10. Pfefferbanm, A.; Zatz, L. M.; Jemigan, T. L. Computer-interactive method for quantifying cerebral spinal fluid and tissue in brain CT scans: Effects of aging. J. Comput. Assist. Tomogr. 10:571-578; 1986.
34
11. Schroth, G.; Nacgele, T.; Klose, U.; Mann, K.; Petersen, D. Reversible brain shrinkage in abstinent alcoholics measured by MRI. Neuroradiology 30:385-389; 1988. 12. SkuUerud, K. Variations in the size of the human brain. Acta Neu-
KROFI" ET AL.
rol. Scand. Suppl. 102:1-112; 1985. 13. Zipursky, R. B.; Lim K. O.; Pfefferbaum, A. MRI study of brain changes with short-term abstinence from alcohol. Alcohol.: Clin. Exp. Res. 13:664-666; 1989.
