Local Cerebral Glucose Utilisation in Chronic Alcoholics: a Positron Tomographic Study
In:
Submitted By JoeBlob Words 1788 Pages 8
Downloaded from http://jnnp.bmj.com/ on November 18, 2015 - Published by group.bmj.com
Journal of Neurology, Neurosurgery, and Psychiatry 1986;49:1165-1170
Local cerebral glucose utilisation in chronic alcoholics: a positron tomographic study
YVES SAMSON,* JEAN-CLAUDE BARON,*t ANDRE FELINE,:
JACQUES BORIES,§ CHRISTIAN CROUZEL*
From Service Hospitalier Frederic Joliot CEA, Departement de Biologie (Orsay),* Clinique des Maladies du
Systeme Nerveux, La Salp&triere,t Service de Psychiatrie, H6pital Kremlin Bicetre,t Service de
Neuroradiologie, La Salpetriere,§ Paris, France
SUMMARY Using positron tomography, a study of regional cerebral glucose utilisation was performed prospectively in a highly selected group of six neurologically unaffected primary chronic alcoholics. In this group, neuropsychological, behavioural and CT scan anomalies were comparable with those previously reported in more extensive studies. With respect to age-matched control values, cerebral metabolic rate was not significantly modified in the selected cortical, subcortical and cerebellar regions of interest. However, the metabolic regional distribution index, which reflects the distribution pattern of glucose utilisation, was selectively and significantly decreased in the mediofrontal area, pointing to a limbic metabolic dysfunction apparently linked to chronic alcoholism.
Even in apparently neurologically unaffected subjects, chronic alcohol abuse may be associated with some degree of cerebral dysfunction. Neuropsychological studies have demonstrated impairment of several motor, spatio-visual and memory functions, despite approximately preserved IQ.' Changes in cerebral blood flow have been also reported.68 Although pathological studies reported only equivocal cortical alterations in chronic alcoholics,5 9 10 the occurrence of widened cortical sulci
(cerebral atrophy) has been demonstrated in vivo by numerous CT scan studies. " - 16 However, the precise mechanism of the reported morphological and neuropsychological changes, and the interrelationships among the two, remain largely unknown.2 Experimentally, alterations of neuronal membranes,17 alteration of dopaminergic and gabaergic systems,'8-2' as well as selective vulnerability of hippocampal neurons,22 23 have been reported, strengthening the hypothesis that alcohol alters neuron function and even perhaps structure. The present study was an attempt to determine by means of positron tomography (PET) if abnormal cerebral glucose utilisation (CMRGIu) could be found in a clinically homogeneous sample of highly selected neurologically unaffected chronic alcoholics.
Address for reprint requests: Yves Samson, Service Hospitalier
Frederic Joliot Hopital d'Orsay, 91406 Orsay, France.
Received 13 August 1985 and in revised form 9 December 1985.
Accepted 15 December 1985
Methods
Six subjects admitted to the psychiatric department of a general hospital were prospectively selected on the following criteria: 30-60 years of age, chronic dependence on alcohol
(DSM III), present hospital admission directly related to alcoholism, right handedness, provision of informed consent. Criteria of exclusion were: preexistent psychiatric, neurological or severe physical disease (including alcoholrelated encephalopathy), head trauma with loss of consciousness, seizures, clinically obvious hepatic cirrhosis or insufficiency and drug abuse.
Neurological and psychiatric clinical examination, including a standardised questionnaire about drinking history and sociobehavioural alterations was performed for each subject, as well as EEG, CT and routine biological laboratory tests. Neuropsychological testing was also performed, including performance and verbal IQ determination, cognitive tasks (Wisconsin Cards Sorting test), Rey's figure copy and delayed reproduction, Weschler memory test or battery 144,24 Luria series.
Using the '8F-fluoro-2-deoxy-D-Glucose ('8FDG) method26 PET studies were carried out on an ECAT II, between the end of the first week and the end of the first month of the hospital admission with apparent abstinence.
Three adjacent brain levels were scanned consecutively
(respectively 15, 35, 55 mm above and parallel to the orbitomeatal line) on subjects at rest, eyes closed, ears unplugged and free from any medication for at least 24 hours, according to our usual protocol.25 Briefly, all images were corrected for attenuation using Ge68-Ga68 transmission scans;
18FDG radioactivity blood curve was obtained from crosscalibrated plasma counting of serial arterial blood samples,
1165
Downloaded from http://jnnp.bmj.com/ on November 18, 2015 - Published by group.bmj.com
1166
Samson, Baron, Feline, Bories, Crouzel
Table Regioncal cerebral nietabolic rate of glucose
MF II
MO !!
Alcoholics
6 16 +
1-23
6-96 +
T I!
LF II
L
R
L
7-36 +
1-35
7-77 +
L
593 + 5-89 + 6-32 + 6-44 + n = 6
1-16
1-17
1-14
1-24
Controls
6-22 + 6-51 + 6-63 + 6-88 + n = 6
1-32
1-35
1-05
1-14
1-03
1-04
Regional cerebral metabolic rate of glucose CMRGlu (mean + SD) expressed subjects. Abbreviations for regions as in fig 1.
collected through a radial arterial catheter. Arterial plasma glucose content was averaged from four samples. The
18FDG cerebral images (2 x 106 counts, each) were scanned
45 to 70 min after the IV injection of 8mCi of 18FDG.
Quantitative CMRGlu images were obtained using the
"autoradiographic" method developed by Phelps and coworkers with values of gray matter FDG rate constants (k,
= 0-102, k2 = 0-13, k3 = 0-062, k4 = 0-0068) and a lumped constant (LC = 0-42) measured by these authors in healthy volunteers.26 In addition, 12 serial scans of the middle brain level were scanned from the end of injection time up to
55 min. This allowed, by means of least-square fitting procedure developed in our laboratory,27 a calculation of the individual regional values of the three FDG rate constants: ki, k2, k3, (k4 being considered as negligible with this method) and the corresponding, supposedly more reliable,
"kinetic" CMRGlu value. The same LC value (0 42) was used. Data analysis In each subject, 30 regional CMRGlu values were obtained from an initial set of 42 standardised 4cm2 circular regions of interest, pooled together in meaningful anatomical areas (fig 1). In addition, for the two upper brain levels, cortical regional distribution index (RDI) were
defined as the ratio of absolute regional value to the corresponding mean cortical value (the mean cortical value being the average value of all symmetrical cortical areas in the corresponding plane). A similar set of data was obtained in a control group consisting of six age-matched subjects (50-2
+ 9-9 years), non alcoholic subjects, who were free from overt dementia or cerebro-vascular risk factors. Statistical analysis was performed region by region using two-tailed
Student t test.
Results
Clinical data Four men and two women were selected. Their mean age (± SD) was 49'8 + 8-2 years
(range 40-59). Reported duration of alcohol intoxication varied from 5 to 25 years (13 + 8) with a usual daily consumption of alcohol ranging from 150 g to
400 g (200 + 98 g). Educational levels were low ( < 5 years), median, or high (> 10 years) in two, three and one subjects, respectively. Four subjects had poor
1
2
3
Fig I Set of circular regions of interest (ROIs) used to define the "anatomical" regions. On Plane I (OM +
15mm) left hand side: Cerebellum (Cb). # 1; Temporal area (TI). 2; On Plane 2, (OM + 35 mm) left hand side: Thalamus (TK) :11; lenticular nucleus (Lt) # 12; Caudate nucleus (Cd) # 10; latero-frontal area (LF
II): # 8, 9; Temporal area (TI!).: 6, 7,- Temporo-occipital area (TO): # 4, 5; occipito-lateral area (LO II).
# 3; The low medio-frontal (MF II mediomedio-occipital (OM II) areas are ROIs # I and 2 respectively; On
Plane 3 (OM + 55mm) left hand side: latero-frontal area (LF III): 9 8, 9; sensori-motor area (SM): # 7, 6; parieto-occipital area: # 4, 5; and occipito-lateral area (OL III): $ 3; The upper medio-frontal (MF III) and medio-occipital (OM III) areas are ROIs I and # 2 respectively; Symmetrical ROIs were automatically copied on the right hemisphere.
:
Downloaded from http://jnnp.bmj.com/ on November 18, 2015 - Published by group.bmj.com
Local cerebral glucose utilisation in chronic alcoholics: a positron tomographic study
MFIII
LF III
MO III
R
L
46 + 640 + 591 +
8-24 +
604 +
38
4-43
1 51
1t05*
0-95
23 + 6-16 + 7-14 +
9-07 +
6-58 +
33
0-93
1-07
0-98
0-87
n this region, statistical significance was nearly
S.M.
P.O.
OL III
TI
Cb
R
L
R
L
R
L
R
L
R
597 + 6-21 + 6-09 + 6-34 + 6-21 + 7-53 + 7-36 + 4-88 + 506 + 6-86 + 6-95 +
0-93
1-10
104
1-05
124
1-10
1-07
0-99
1-08
1-07
1-11
6-61 + 7-10 + 7-17 + 6-64 + 6-87 + 8-25 ± 8-07 + 5-36 + 5-67 + 7-03 + 7-16 +
0-74
1-5
1-24
0-91
0-92
0-7
0-87
0-51
0-59
1-26
1-08
reached: (p = 0-07).
R
L
socioprofessional adjustment. None of the subjects had persistent withdrawal signs at the time of study, although two patients did experience some initially.
The sole abnormal neurological finding was asymptomatic polyneuritis in two subjects. No significant anomalies were detected by EEG. At admission gamma-amino-glutamyl transferase levels were markly increased in five subjects and RBC macrocytosis was found in all six subjects; coagulation tests were normal in each case.
The CT scans were analysed according to established criteria modified from Lishman.5 Using this scale, widening of cortical sulci was marked, moderate or absent in two, three and one patients, respectively.
Mild widening of the interhemispheric fissure was found in two patients. Enlargement of lateral ventricles was moderate in three subjects and questionable in two.
0 Alcoholics
Neuropsychological examination Cognitive and intellectual functions were normal in five subjects and moderately impaired in one. Four subjects had visuoconstructional difficulties. Graphic and gestural Luria tests (studied in five subjects) were impaired in three patients. Memory impairment was detected in four subjects, affecting predominantly visual memory in two subjects. It must be stressed however, that this memory impairment was of a very mild degree compared with, for example, Wernicke-Korsakoff psychosis.28 Regional cerebral glucose utilisation Although cortical regional CMRGlu values were slightly lower in alcoholics than in controls, the differences never reached statistical significance (table). However, in the upper medio-frontal region, the CMRGlu was reduced by 17% in alcoholics just short of statistical significance (p = 0-07). In subcortical regions and in
