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Assessment of cortical brain blood flood by brain perfusion SPECT in patients with a diagnosis of eating behavior disorders
original articles
Assessment of cortical brain blood flood by brain perfusion SPECT in patients with a diagnosis of eating behavior disorders V.M. POBLETE GARCÍAa, A. GARCÍA VICENTEa, A. SORIANO CASTREJÓNa, L. BEATO FERNÁNDEZb, I. GARCÍA-VILCHESb, T. RODRÍGUEZ-CANOb, M. CORTÉS ROMERAa, S. RUIZ SOLÍSa, S. RODADO MARINAa AND M.P. TALAVERA RUBIOa a
Nuclear Medicine and bPsychiatry Departments. Hospital General de Ciudad Real. Spain.
Abstract.—Objective. To evaluate cortical brain blood flow by 99mTc-HMPAO SPECT in patients with Eating Disorders (ED): restrictive anorexia (RA) and purgative bulimia (PB).
Material and method. The study included 7 women with diagnostic criteria of RA and 12 with PB. The control group was made up of 12 healthy women. All subjects underwent brain 99m Tc-HMPAO SPECT. The SPECT studies were quantified, yielding semiquantitative indexes relating to cerebellar activity in different regions. Body dissatisfaction was assessed by means of the BSQ (Body Shape Questionnaire). The results were analyzed with the ANOVA variance and had a statistical significance of p < 0.05. Results. Mean BSQ scores were 98.28 (range 71-159) in the RA group, 145.05 (range 73-191) in the PB group, and 57.4 (range 37-88) in the control group. All patients in the sample (i.e., both RA and PB) showed global cerebral hypoperfusion versus the controls, although the difference only reached statistical significance in the RA group in the left parietal lobe (p = 0.02) and in the right (p = 0.004) and left temporal lobes (p = 0.015). In the PB group, the significantly hypoperfused regions were the right (p < 0.001) and left (p = 0.008) superior frontal lobe, the right inferior frontal lobe (p = 0.042), the right (p = 0.042) and left (p = 0.002) parietal lobes, and the right temporal lobe (p = 0.002). Conclusion. The results obtained showed that patients with ED had cerebral hypoperfusion compared with healthy subjects. This pattern is common in parietotemporal regions for both PB and AR although with temporal and parietal predominance in RA and PB, respectively. In addition, patients with PB had frontal region involvement. KEY WORDS: eating disorders, restrictive anorexia, purgative bulimia, HMPAO SPECT, Body Shape Questionnaire.
VALORACIÓN DEL FLUJO CORTICAL CEREBRAL MEDIANTE SPECT DE PERFUSIÓN CEREBRAL EN PACIENTES CON DIAGNÓSTICO DE TRASTORNOS DE LA CONDUCTA ALIMENTARIA Resumen.—Objetivo. Valorar el flujo cortical cerebral mediante 99mTc-HMPAO SPECT en pacientes con trastornos de la conducta alimentaria (TCA): anorexia restrictiva (AR) y bulimia purgativa (BP). Material y método. Se estudiaron 7 mujeres con criterios de AR y 12 de BP. Se constituyó un grupo control de 12 mujeres sanas, realizando un estudio de SPECT cerebral con 99mTc-HMPAO. Se obtuvieron índices semicuantitativos respecto a cerebelo en regiones frontales superiores, inferiores, parietales, temporales y occipitales. Se valoró la insatisfacción corporal con el BSQ (Body Shape Questionnaire). El análisis de los datos se realizó utilizando la varianza de un factor (ANOVA), con un nivel de significación estadística de p < 0,05. Resultados. Los valores medios obtenidos en el BSQ fueron de 98,28 (71-159) en el grupo de las AR, de 145,05 (73-191) en las BP y de 57,4 (37-88) en el grupo control. En sujetos normales se evidenció un predominio fisiológico de la perfusión en hemisferio derecho, más evidente en lóbulos temporales (11 %). Se evidenció una menor actividad global en todas las regiones corticales en el conjunto de los pacientes respecto al grupo control, aunque sólo significación estadística en lóbulo parietal izquierdo (p = 0,02), y lóbulos temporales derecho (p = 0,004) e izquierdo (p = 0,015) en las AR, y en lóbulos frontal superior derecho (p < 0,001) e izquierdo (p = 0,008), frontal inferior derecho (p = 0,042), parietales derecho (p = 0,042) e izquierdo (p = 0,002) y temporal derecho (p = 0,002) en las BP. Conclusión. Las pacientes con TCA mostraron una significativa hipoperfusión cortical respecto al grupo control en regiones parietotemporales, con predominio en lóbulo temporal en AR y en parietal en BP. Además, las pacientes con BP mostraron afectación concomitante de regiones frontales. PALABRAS CLAVE: trastorno de la conducta alimentaria, anorexia restrictiva, bulimia purgativa, HMPAO SPECT, Body Shape Questionnaire.
Received: 2-5-06. Accepted: 9-10-06. Correspondence: V.M. POBLETE GARCÍA Servicio de Medicina Nuclear Hospital General de Ciudad Real Tomelloso, s/n. 13005. Ciudad Real (Spain) E-mail: [email protected]
INTRODUCTION
The concept of eating behavior disorders (ED) encompasses a series of psychiatric conditions in which
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patients commonly display excessive anxiety and concern about body weight and physical appearance. In these patients, eating acquires special importance and every thought and act in their daily lives centers on eating and patients feel completely dependent on this idea. Anorexia nervosa (AN) is a syndrome characterized by the patient’s refusal to maintain a normal minimum body weight; the patient induces weight loss and maintains it deliberately due to intense fear of gaining weight. In addition, these patients have a significantly disturbed perception of their body shape or size. Within AN, two subgroups are differentiated by the measures used to avoid weight gain: the restrictive subtype, in which weight is lost by strict dieting, fasting, or intense exercise, and the compulsive subtype, in which the patient has episodes of overeating and compensates for it by methods such as self-induced vomiting, laxative and/or diuretic use, and others. The other major syndrome included in the ED is bulimia nervosa (BN), which has been defined as a condition separate from AN for only about 25 years,1 although it had been known and defined for decades earlier.2 Patients with this condition are characterized as being obsessively concerned with food, having an irresistible and uncontrollable desire to eat with episodes of overeating in which large amounts of food are consumed in a very short time, who feel that they have lost voluntary control. In order to compensate for this conduct, patients resort to unsuitable methods to avoid weight gain, such as self-induced vomiting and abuse of laxatives, diuretics, enemas, etc. As occurs in AN, BN is subdivided into two subgroups: the purgative subtype, in which patients induce vomiting and use laxatives, diuretics and enemas, and the nonpurgative subtype, in which the compensatory mechanisms used are others, such as fasting and intense physical exercise. The pathogenesis of ED remains unknown. Nevertheless, numerous studies indicate that they are associated to cerebral dysfunction. Whether these disturbances are due to nutritional disorders or are a specific biological marker of these conditions is still debated. Development of techniques in nuclear medicine like positron emission tomography (PET) or SPECT has made it possible to evaluate both metabolism and cerebral perfusion in vivo. As numerous studies have demonstrated a narrow relation between neuronal 12
activity and central nervous system blood flow, calculation of cerebral cortical flow can reflect regional neuronal activity.3 Functional neuroimaging studies have been used to evaluate brain function in EBD under baseline conditions, as well as after subjecting patients to different specific stimuli, such as exposure to their body silhouette, food intake, or simply viewing these stimuli. The findings in patients with AN and BN described in these studies show certain similarities and differences compared to other studies.4 For that reason, there is still a debate between those who think that ED are a single pathologic entity with different clinical manifestations and those that think that AN and BN are completely different syndromes.5,6 The aim of our study was to evaluate the pattern of cerebral cortical blood flow of patients with EBD in different stages of evolution compared to a group of control subjects, and to identify any differences between patients who meet criteria for restrictive anorexia (RA) and purgative bulimia (PB).
MATERIAL AND METHODS
Study subjects
We made a prospective study in which the case sample was constituted by a total of 19 female patients diagnosed as having EBDs. Seven of them presented RA criteria according to the DSM-IV (mean age 25 years, range 19-36 years) and 12 patients presented PB criteria (mean age 28 years, range 18-42 years). These patients presented different degrees of evolution of their disorders. None of them had symptoms of another type of neuropsychiatric disease. A total of 9 patients with PB and 4 with RA were under treatment for their condition when the study was made. Antidepressants were administered to 6 patients with PB and to 1 with RA, and an association of antidepressants and benzodiazepines to 3 patients with PB. This medication was not discontinued for ethical reasons. Epidemiologic information was collected from all patients, such as age, height, and weight; the last two are used to calculate body mass index (BMI) (Table 1). BMI is a value used to determine the healthiest weight range for a person using height and weight. According to the WHO, a range of 18.5 to 24.9 is healthy. A BMI lower than 18.5 indicates malnutrition, whereas 25 to 29.9 indicates overweight or grade 1 obesity. From
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Poblete García VM et al. Assessment of cortical brain blood flood by brain perfusion SPECT in patients with a diagnosis of eating behavior disorders
30 to 39.9, mild, or grade 2, obesity exists, and from 40 on, morbid, or grade 3, obesity. Information could not be obtained on the time of evolution of the disease, given the circumstances typical of these conditions: denial of illness by patients and concealment of practices to avoid weight gain. The patient’s dissatisfaction with her body was evaluated using the Body Shape Questionnaire (BSQ), which was designed by Cooper et al.7 and adapted to the Spanish population by Raich et al.8 The BSQ showed a high validity that concurred with similar instruments, such as the corporal dissatisfaction subscale of the Eating Disorders Inventory (EDI).9 This questionnaire consisted of 34 items related to self image that are evaluated using a six-point frequency scale (1=never, 2=rarely, 3=sometimes, 4=often, 5=frequently, 6=always). Therefore, the range of scores is 34-204, threshold values of 105 or more being considered pathologic. The factors evaluated are: corporal dissatisfaction, fear of getting fat, feelings of low self-esteem due to appearance, and desire to lose weight. The control group was constituted by a total of 12 healthy women with no history of psychiatric or neurologic disease or of drug consumption. The mean age of the control group was 20 years (range 18-27 years). All study subjects, both patients and controls, were right-handed. The study was authorized by the hospital ethics committee. An informed consent form was signed by each study subject after receiving an explanation of the methodology to be used. Before performing scintigraphic scans, pregnancy was excluded by a specific test. SPECT procedure and quantitation
After the study subjects had rested for at least thirty minutes in a quiet room, a bolus of 99mTchexamethylpropyleneamine oxime, 99mTc-HMPAO (Ceretec®, Amersham Health), with an activity of 740 MBq, was injected through a cannula in antecubital vein, The radiopharmaceutical was prepared in strict accordance with the manufacturer’s instructions and administered within 15 minutes of preparation. Scan acquisition began within 30 minutes of injection. The scan was made with an Infinia Hawkeye® model (General Medical Electric Systems, Milwaukee, Wis) double-head scintigraph with an intrinsic spatial
Table 1. DISTRIBUTION OF THE SUBJECTS IN THE SAMPLE Ident.
Diag.
Age
BMI
BSQ
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
Control Control Control Control Control Control Control Control Control Control Control Control RA RA RA RA RA RA RA PB PB PB PB PB PB PB PB PB PB PB PB
23 19 19 21 28 19 21 19 19 19 21 19 24 20 18 26 23 37 24 28 31 19 24 24 35 36 18 43 32 24 30
24 20 19 22 19 23 21 24 22 23 20 21 21 19 15 17 19 18 18 19 29 19 29 20 28 22 20 23 22 20 22
44 40 68 62 37 43 48 75 88 86 38 60 80 74 90 71 159 96 118 183 111 73 191 181 148 136 164 177 86 177 114
Age, body mass index (BMI) and BSQ score (Body Shape Questionnaire) of the subjects in the sample. Diag: group diagnosis; RA: restrictive anorexia; PB: purgative bulimia.
resolution in the central field of vision (CFOV) of 3.8 mm FWHM (Full-Width Half-Maximum). Parallel, low-energy, high-resolution (LEHR) collimators were used. The acquisition matrix was 64x64, with a 1.0 zoom. The acquisition orbit was a 360º circle in which 60 images were acquired (30 per head), each lasting 30 seconds. “Step & shoot” acquisition was used. Under these conditions, a slice thickness of 8.84 mm was obtained. Scans were processed by filtered retroprojection using a Metz filter (FWHM: 1.9; order 4.6). Image reorientation was performed, obtaining images from slices parallel to the orbitomeatal axis and sagittal and coronal slices. The Segami Neuromatching quantitation program was used. This program yields regions of interest (ROIs) semiautomatically: on transaxial images, the outer and inner limits of cortical activity are delimited manually. After this operation is performed, the
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Poblete García VM et al. Assessment of cortical brain blood flood by brain perfusion SPECT in patients with a diagnosis of eating behavior disorders
Fig. 1.—Images of transaxial slices showing the cortical regions of interest (ROIs) obtained by the semiautomatic quantitation method. Semiquantitative indices of cortical activity in these ROIs were obtained, taking cerebellar activity as a reference.
program automatically divides the cerebral cortex into ROIs. This process was applied to 8 successive transaxial slices, including almost all of the cortical regions (Fig. 1). Once these segments were obtained, the activity of 10 cortical regions was calculated from the mean count per pixel of the ROIs corresponding to the upper and lower frontal, parietal, temporal and occipital cortices of the right and left hemispheres. Regular elliptical ROIs also were applied manually to both cerebellar hemispheres. The activities of each cerebral region and the cerebellar hemispheres were obtained as mean counts per pixel. The cerebellar count, consisting of the mean count per average pixel of each cerebellar hemisphere, was used as the reference activity. Later, semiquantitative indices of cerebral cortical activity and cerebellar activity were calculated using the formula [(mean count per pixel in cortical ROIs/mean count per average pixel of both cerebellar hemispheres) x 100]. These indices were evaluated and compared statistically between the control group and patients 14
with EBD, and between RA and PB patients in the EBD group. Statistical analysis
Data were analyzed using analysis of variance of a factor (ANOVA) to evaluate the differences in mean uptake between RA and PB groups in relation to normal subjects. The same method was used to evaluate the possible influence of drug treatment on cerebral perfusion in treated versus untreated patients and the difference between types of treatment in the group of treated patients. The statistical significance level was p<0.05.
RESULTS
Mean BMI values calculated in the patients were 18.14 in the RA group (range 15-21) and 22.75 in the PB group (range 19-29). In the control group, mean
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Poblete García VM et al. Assessment of cortical brain blood flood by brain perfusion SPECT in patients with a diagnosis of eating behavior disorders Table 2. DISTRIBUTION OF MEANS AND 95% CONFIDENCE INTERVALS OF THE CORTICAL ACTIVITY INDICES OBTAINED IN DIFFERENT CEREBRAL REGIONS ROI Right upper frontal
Control
RA
PB
110.1 (97.8-102.5)
94.4 (89.3-99.5)
93.06 (90.4-95.6)
Left upper frontal
91.5 (89.3-93.7)
88.1 (83.8-92.4)
86.40 (83.8-88.9)
Right lower frontal
99.0 (96.5-101.5)
94.8 (91.4-98.2)
95.30 (93.6-96.9)
Left lower frontal
90.8 (88.4-93.1)
88.2 (84.9-91.4)
89.30 (87.9-90.6)
Right parietal
91.2 (89.3-93.2)
87.0 (83.2-90.8)
86.10 (83.8-88.3)
Left parietal
82.1 (80.1-84.06)
76.4 (72.9-80)
77.20 (75.2-79.2)
Right temporal
93.6 (91.7-95.5)
88.4 (85.9-90.9)
89.50 (88.2-90.9)
Left temporal
83.1 (79.9-83.5)
78.2 (75.3-81.1)
81.70 (79.9-83.5)
Right occipital
93.7 (91.3-96.1)
89.7 (87-92.5)
91.10 (89.2-93.04)
Left occipital
88.9 (87.2-90.6)
85.0 (81.6-88.3)
88.20 (85.8-90.6)
In bold, the regions that showed statistically significant differences in patients versus control subjects. ROI: regions of interest; RA: restrictive anorexia; PB: purgative bulimia.
BMI was 21.5 (range 19-24). Mean BSQ score (Table 1) was 98.28 (range 71-159) in the RA group and 145.08 (range 73-191) in the PB group. In the group of control subjects, these values were 57.4 (range 3788). Cerebral cortical perfusion analyzed using the equation (right lobe activity/left lobe activity) x 100 disclosed more activity in the control group subjects in the right lobes than in the left lobes. The difference was more marked in the temporal lobes, with 11% more activity in the right lobes than in the left, and less marked in the occipital lobes, where the difference was only 5%. In the EBD patient group, comparison of the mean activity of each cortical region to the control group showed lower values in both RA and PB patients in all of the cortical regions studied. Statistical analysis of these differences revealed that they were statistically significant in the left parietal (p=0.020), right temporal (p=0.004) and left temporal lobes (p=0.015) of the RA group and in the right upper frontal (p<0.001), left upper frontal (p=0.008), right lower frontal (p=0.042), right parietal (p=0.002), left parietal (p=0.002), and right temporal (p=0.002) of the PB group. The 95% confidence intervals of the mean uptakes in each cerebral region of the three study groups are shown in Table 2. With respect to medication, there was no difference in the distribution of cerebral blood flow between medicated and nonmedicated patients. In the medicated patients there were no differences between those treated
with antidepressants alone and those treated with a combination of antidepressants and benzodiazepines (ANOVA: p>0.05).
DISCUSSION
In cerebral perfusion studies it is important to know the normal pattern of distribution of a radiopharmaceutical to evaluate significant alterations in any neuropsychiatric condition. In this sense, many studies report an asymmetrical radioisotope distribution with predominance of the right hemisphere over the left hemisphere.10-13 In addition, this asymmetry has been observed to increase with age, the greatest difference between right and left side being found in subjects age 60 to 70 years.14 The results of our control group subjects coincide with these studies because we found more perfusion in all of the regions of the right hemisphere compared to the left hemisphere, particularly in the temporal lobes. EBDs are complex processes in which biological, emotional and behavioral components converge in the pathophysiology. These patients commonly suffer other disorders, such as major depression15,16 or obsessive-compulsive disease traits.17 Nonetheless, the pathogenesis of these conditions is still unknown. There is evidence of a neuronal disorder in these conditions because the clinical syndrome can be reproduced by injury to the right lower prefrontal cortex.18,19 The fact that perinatal complications are associated with the development of these conditions
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Poblete García VM et al. Assessment of cortical brain blood flood by brain perfusion SPECT in patients with a diagnosis of eating behavior disorders
also is suggestive of an organic cerebral substrate.20 In addition, the findings obtained with neuropsychologic, electrophysiologic and neuropharmacologic techniques and functional and structural neuroimaging suggest the existence of an underlying neural disorder21. Kornreich et al.22 reported an increase in the size of the cerebral ventricles in AN-diagnosed adolescent children compared with healthy controls, but the difference did not reach statistical significance. Husain et al.23 found a significantly smaller thalamus and middle cerebral regions in patients with anorexia compared to control subjects and to patients with bulimia. The comparison of mean cortical activity values in our study showed that mean cortical activity in these patients, both the RA and PB subgroups, is lower in all cortical regions. Similar findings have been reported in earlier studies, such as that of Delvenne et al.24 with PET, in which overall cerebral hypometabolism was reported. However, this hypoperfusion was only statistically significant in some regions, these differences being related to the type of eating disorder the patients had: in patients with RA, statistically significant hypoperfusion was seen in both temporal lobes and the left parietal lobe, whereas in patients with PB we found a more generalized and significant involvement, with hypoperfusion in bilateral parietal lobes, the right temporal and upper frontal and right lower frontal cortex. These findings concur in part with those obtained by the Delvenne group, discussed previously, because the hypometabolism described in patients with AN predominated in the parietal and frontal regions, which was not found in our study group. More recently, the same group described hypometabolism in the parietal regions of patients with AN as well as BN criteria,25 which does agree with our findings. Our results also show certain similarities with those of other studies. For instance, Gordon et al.26 observe marked asymmetry between the temporal lobes in 13 of 15 patients with AN, 8 with left-sided and 5 with right-sided hypoperfusion. These findings persisted in 3 of the patients in which the study was repeated after weight was restored. This fact suggests the existence of an underlying organic condition. However, this group found no disturbance in the parietal regions, in contrast with our findings. In a group of 21 patients with AN (19 women and 2 men) of an age similar to the women in our sample, in which 19 had recovered their weight, Rastam et al.27 evaluated cerebral cortical blood flow by 99mTc16
HMPAO SPECT. They observed hypoperfusion of the temporoparietal regions and orbitofrontal cortex long after normal weight was regained. Although there is no clear explanation for this temporoparietal affectation, given the similarity with the findings described in these studies, these alterations seem to be a consequence of neurophysiologic or morphologic aspects of ED.28 Impaired frontal perfusion in patients with AN has been reported by other groups, such as Takano et al.29 and Naruo et al.30, who found diminished perfusion of the anterior cingulate gyrus circumvolution of bilateral nature in patients with RA. These authors claim that these findings suggest that hypoperfusion of the frontal cortex, which includes the anterior cingulate gyrus, could be associated with both the implacable desire that these patients have to be thin and their altered perception of their body image. This claim could explain why we did not encounter significant hypoperfusion of the frontal cortex in the group of patients diagnosed as RA, whereas this finding was present in patients with PB, since the group of bulimic women showed clearly abnormal BSQ scores (>105), which was indicative of more corporal dissatisfaction, whereas the group of anorexic women, which were the majority, presented scores below the limit of pathology. These data may be suggestive of a certain relation between frontal hypoperfusion and corporal dissatisfaction, fear of gaining weight and a wish to lose weight in bulimic patients, a finding not seen in patients with RA. With regard to frontal perfusion abnormalities, Nozoe et al.,31 in a study of patients with AN and BN, obtained results that were the opposite of those seen in our study because they demonstrated increased perfusion of inferior frontal regions in patients with BN compared to both the AN group and control group. In the same group, when the perfusion study was repeated after food intake, it showed increased perfusion in the upper and lower frontal regions of patients with AN, but no changes in the patients with BN. One possible explanation for this finding would be the relation between the frontal cortex, hypothalamus, and appetite control mechanisms.32 Absence of change in the lower frontal areas in patients with BN after intake could be related to a deficient function of the satiety mechanism, which would be secondary to hyperphagia in these patients. For example, it has been reported that frontal lobe lesions produce secondary hyperphagia.33 In contrast, the increase in frontal
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perfusion after intake in patients with AN is related to an overactive system of satiety control. This explains the hypophagia typical of these patients. In relation to our findings, the hypoperfusion demonstrated in frontal regions in our patients with BN could be related to this hypothetical deficiency in satiety system function, although it is impossible to draw conclusions in light of the nonspecificity and incongruence of the findings and the small number of patients studied. It is interesting to emphasize that most semiquantitative studies of cerebral cortical perfusion in patients with EBD use cerebellar activity as a reference because the alterations produced by these conditions affect the cerebral cortex exclusively.34 However, Addolorato et al.35 encountered diminished cortical perfusion of the temporo-parieto-occipital regions of an asymmetrical nature in a young woman diagnosed as AN. In addition, there is an important decrease in the perfusion of the left cerebellar hemisphere, which was visualized as smaller than the opposite cerebellar hemisphere. Computed tomography (CT) showed increased external cerebrospinal spaces, asymmetrical cerebral atrophy without focal parenchymal lesions, and marked cerebellar atrophy. These findings suggest that cerebellar alterations can be found in patients with certain forms of AN, although this was not so in our case because all the subjects in our sample showed sustained, symmetrical uptake by the cerebellar hemispheres, thus validating the use of this activity as a reference in the calculation of semiquantitative indices of cerebral cortical activity. We cannot discuss CT findings because this study was not performed in any participants, whether control subjects or patients. CT is performed only in patients in whom the symptoms suggest organic neurologic damage, which did not occur in any of our patients. The limitations of our study were, on the one hand, the inclusion of patients with pharmacologic treatment in our sample, which could have affected the results. However, we found no statistically significant differences between treated and untreated patients and between treated patients who took one type of medication or another. On the other hand, the small number of subjects in our sample precludes definitive conclusions, although other study samples in the bibliography had results similar to ours. In conclusion, patients with ED, whether RA or PB, showed a pattern of overall cerebral hypoperfusion compared to the control group. This hypoperfusion was more significant in the temporoparietal regions,
although there was more temporal lobe affectation in the case of patients with RA and more parietal affectation in PB. These findings could be considered a specific biological marker in these patients because they were seen in patients with different degrees of evolution of their symptoms. Nevertheless, the frontal cortical hypoperfusion that was demonstrated exclusively in patients with PB could be related more with the patient’s degree of dissatisfaction with body image, which was clearly changed in patients with PB but not in patients with RA.
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25. Delvenne V, Goldman S, De Maertealer V, Lotstra F. Brain glucose metabolism in eating disorders assessed by positron emission tomography. Int J Eat Disord. 1999;25:29-37. 26. Gordon I, Lask B, Bryant-Waugh R, Christie D, Timimi S. Childhood-onset anorexia nervosa: towards identifying a biological substrate. Int J Eat Disord. 1997;22:159-65. 27. Rastam M, Bjure J, Vestergren E, Uvebrant P, Gillberg IC, Wentz E, et al. Regional cerebral blood flow in weight-restored anorexia nervosa: a preliminary study. Dev Med Child Neurol. 2001;43: 239-42. 28. Garfinkel P, Kennedy SH, Kaplan AS. Views on classification and diagnosis of eating disorders. Can J Psychiatry. 1995;40: 445-56. 29. Takano A, Shiga T, Kitagawa N, Koyama T, Katoh C, Tsukamoto E, et al. Abnormal neuronal network in anorexia nervosa studied with I-123-IMP SPECT. Psychiatry Res. 2001;107:45-50. 30. Naruo T, Nakabeppu Y, Deguchi D, Nagai N, Tsutsui J, Nakajo M, et al. Decreases in blood perfusion of the anterior cingulate gyri in anorexia nervosa restricters assessed by SPECT image analysis. BMC Psychiatry. 2001;1:2-6. 31. Nozoe S, Naruo T, Yonekura R, Nakabeppu Y, Soejima Y, Nagai N, et al. Comparison of regional cerebral blood flow in patients with eating disorders. Brain Res Bull. 1995;36:251-5. 32. Oomura Y, Ono T, Ohta M, Nishino H, Shimizu N, Ishibashi S, et al. Neuronal activity in feeding behaviour of chronic monkeys. En: Katsuki, Y, Sato M, Takagi S, Oomura Y, editors. Food intake an chemical senses. Tokyo: Tokyo University of Tokyo press; 1977. p. 373-5. 33. Fuster JM. The prefrontal cortex. 2nd ed. New York: Raven; 1989. 34. Herholz K. Neuroimaging in anorexia nervosa. Psychiatry Res. 1996;62:105-10. 35. Addolorato G, Taranto C, Capristo E, Gasbarrini G. A case of marked cerebellar atrophy in a woman with anorexia nervosa and cerebral atrophy and a review of the literature. Int J Eat Disord. 1998;24:443-7.
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Assessment of cortical brain blood flood by brain perfusion SPECT in patients with a diagnosis of eating behavior disorders V.M. POBLETE GARCÍAa, A. GARCÍA VICENTEa, A. SORIANO CASTREJÓNa, L. BEATO FERNÁNDEZb, I. GARCÍA-VILCHESb, T. RODRÍGUEZ-CANOb, M. CORTÉS ROMERAa, S. RUIZ SOLÍSa, S. RODADO MARINAa AND M.P. TALAVERA RUBIOa a
Nuclear Medicine and bPsychiatry Departments. Hospital General de Ciudad Real. Spain.
Abstract.—Objective. To evaluate cortical brain blood flow by 99mTc-HMPAO SPECT in patients with Eating Disorders (ED): restrictive anorexia (RA) and purgative bulimia (PB).
Material and method. The study included 7 women with diagnostic criteria of RA and 12 with PB. The control group was made up of 12 healthy women. All subjects underwent brain 99m Tc-HMPAO SPECT. The SPECT studies were quantified, yielding semiquantitative indexes relating to cerebellar activity in different regions. Body dissatisfaction was assessed by means of the BSQ (Body Shape Questionnaire). The results were analyzed with the ANOVA variance and had a statistical significance of p < 0.05. Results. Mean BSQ scores were 98.28 (range 71-159) in the RA group, 145.05 (range 73-191) in the PB group, and 57.4 (range 37-88) in the control group. All patients in the sample (i.e., both RA and PB) showed global cerebral hypoperfusion versus the controls, although the difference only reached statistical significance in the RA group in the left parietal lobe (p = 0.02) and in the right (p = 0.004) and left temporal lobes (p = 0.015). In the PB group, the significantly hypoperfused regions were the right (p < 0.001) and left (p = 0.008) superior frontal lobe, the right inferior frontal lobe (p = 0.042), the right (p = 0.042) and left (p = 0.002) parietal lobes, and the right temporal lobe (p = 0.002). Conclusion. The results obtained showed that patients with ED had cerebral hypoperfusion compared with healthy subjects. This pattern is common in parietotemporal regions for both PB and AR although with temporal and parietal predominance in RA and PB, respectively. In addition, patients with PB had frontal region involvement. KEY WORDS: eating disorders, restrictive anorexia, purgative bulimia, HMPAO SPECT, Body Shape Questionnaire.
VALORACIÓN DEL FLUJO CORTICAL CEREBRAL MEDIANTE SPECT DE PERFUSIÓN CEREBRAL EN PACIENTES CON DIAGNÓSTICO DE TRASTORNOS DE LA CONDUCTA ALIMENTARIA Resumen.—Objetivo. Valorar el flujo cortical cerebral mediante 99mTc-HMPAO SPECT en pacientes con trastornos de la conducta alimentaria (TCA): anorexia restrictiva (AR) y bulimia purgativa (BP). Material y método. Se estudiaron 7 mujeres con criterios de AR y 12 de BP. Se constituyó un grupo control de 12 mujeres sanas, realizando un estudio de SPECT cerebral con 99mTc-HMPAO. Se obtuvieron índices semicuantitativos respecto a cerebelo en regiones frontales superiores, inferiores, parietales, temporales y occipitales. Se valoró la insatisfacción corporal con el BSQ (Body Shape Questionnaire). El análisis de los datos se realizó utilizando la varianza de un factor (ANOVA), con un nivel de significación estadística de p < 0,05. Resultados. Los valores medios obtenidos en el BSQ fueron de 98,28 (71-159) en el grupo de las AR, de 145,05 (73-191) en las BP y de 57,4 (37-88) en el grupo control. En sujetos normales se evidenció un predominio fisiológico de la perfusión en hemisferio derecho, más evidente en lóbulos temporales (11 %). Se evidenció una menor actividad global en todas las regiones corticales en el conjunto de los pacientes respecto al grupo control, aunque sólo significación estadística en lóbulo parietal izquierdo (p = 0,02), y lóbulos temporales derecho (p = 0,004) e izquierdo (p = 0,015) en las AR, y en lóbulos frontal superior derecho (p < 0,001) e izquierdo (p = 0,008), frontal inferior derecho (p = 0,042), parietales derecho (p = 0,042) e izquierdo (p = 0,002) y temporal derecho (p = 0,002) en las BP. Conclusión. Las pacientes con TCA mostraron una significativa hipoperfusión cortical respecto al grupo control en regiones parietotemporales, con predominio en lóbulo temporal en AR y en parietal en BP. Además, las pacientes con BP mostraron afectación concomitante de regiones frontales. PALABRAS CLAVE: trastorno de la conducta alimentaria, anorexia restrictiva, bulimia purgativa, HMPAO SPECT, Body Shape Questionnaire.
Received: 2-5-06. Accepted: 9-10-06. Correspondence: V.M. POBLETE GARCÍA Servicio de Medicina Nuclear Hospital General de Ciudad Real Tomelloso, s/n. 13005. Ciudad Real (Spain) E-mail: [email protected]
INTRODUCTION
The concept of eating behavior disorders (ED) encompasses a series of psychiatric conditions in which
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Poblete García VM et al. Assessment of cortical brain blood flood by brain perfusion SPECT in patients with a diagnosis of eating behavior disorders
patients commonly display excessive anxiety and concern about body weight and physical appearance. In these patients, eating acquires special importance and every thought and act in their daily lives centers on eating and patients feel completely dependent on this idea. Anorexia nervosa (AN) is a syndrome characterized by the patient’s refusal to maintain a normal minimum body weight; the patient induces weight loss and maintains it deliberately due to intense fear of gaining weight. In addition, these patients have a significantly disturbed perception of their body shape or size. Within AN, two subgroups are differentiated by the measures used to avoid weight gain: the restrictive subtype, in which weight is lost by strict dieting, fasting, or intense exercise, and the compulsive subtype, in which the patient has episodes of overeating and compensates for it by methods such as self-induced vomiting, laxative and/or diuretic use, and others. The other major syndrome included in the ED is bulimia nervosa (BN), which has been defined as a condition separate from AN for only about 25 years,1 although it had been known and defined for decades earlier.2 Patients with this condition are characterized as being obsessively concerned with food, having an irresistible and uncontrollable desire to eat with episodes of overeating in which large amounts of food are consumed in a very short time, who feel that they have lost voluntary control. In order to compensate for this conduct, patients resort to unsuitable methods to avoid weight gain, such as self-induced vomiting and abuse of laxatives, diuretics, enemas, etc. As occurs in AN, BN is subdivided into two subgroups: the purgative subtype, in which patients induce vomiting and use laxatives, diuretics and enemas, and the nonpurgative subtype, in which the compensatory mechanisms used are others, such as fasting and intense physical exercise. The pathogenesis of ED remains unknown. Nevertheless, numerous studies indicate that they are associated to cerebral dysfunction. Whether these disturbances are due to nutritional disorders or are a specific biological marker of these conditions is still debated. Development of techniques in nuclear medicine like positron emission tomography (PET) or SPECT has made it possible to evaluate both metabolism and cerebral perfusion in vivo. As numerous studies have demonstrated a narrow relation between neuronal 12
activity and central nervous system blood flow, calculation of cerebral cortical flow can reflect regional neuronal activity.3 Functional neuroimaging studies have been used to evaluate brain function in EBD under baseline conditions, as well as after subjecting patients to different specific stimuli, such as exposure to their body silhouette, food intake, or simply viewing these stimuli. The findings in patients with AN and BN described in these studies show certain similarities and differences compared to other studies.4 For that reason, there is still a debate between those who think that ED are a single pathologic entity with different clinical manifestations and those that think that AN and BN are completely different syndromes.5,6 The aim of our study was to evaluate the pattern of cerebral cortical blood flow of patients with EBD in different stages of evolution compared to a group of control subjects, and to identify any differences between patients who meet criteria for restrictive anorexia (RA) and purgative bulimia (PB).
MATERIAL AND METHODS
Study subjects
We made a prospective study in which the case sample was constituted by a total of 19 female patients diagnosed as having EBDs. Seven of them presented RA criteria according to the DSM-IV (mean age 25 years, range 19-36 years) and 12 patients presented PB criteria (mean age 28 years, range 18-42 years). These patients presented different degrees of evolution of their disorders. None of them had symptoms of another type of neuropsychiatric disease. A total of 9 patients with PB and 4 with RA were under treatment for their condition when the study was made. Antidepressants were administered to 6 patients with PB and to 1 with RA, and an association of antidepressants and benzodiazepines to 3 patients with PB. This medication was not discontinued for ethical reasons. Epidemiologic information was collected from all patients, such as age, height, and weight; the last two are used to calculate body mass index (BMI) (Table 1). BMI is a value used to determine the healthiest weight range for a person using height and weight. According to the WHO, a range of 18.5 to 24.9 is healthy. A BMI lower than 18.5 indicates malnutrition, whereas 25 to 29.9 indicates overweight or grade 1 obesity. From
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Poblete García VM et al. Assessment of cortical brain blood flood by brain perfusion SPECT in patients with a diagnosis of eating behavior disorders
30 to 39.9, mild, or grade 2, obesity exists, and from 40 on, morbid, or grade 3, obesity. Information could not be obtained on the time of evolution of the disease, given the circumstances typical of these conditions: denial of illness by patients and concealment of practices to avoid weight gain. The patient’s dissatisfaction with her body was evaluated using the Body Shape Questionnaire (BSQ), which was designed by Cooper et al.7 and adapted to the Spanish population by Raich et al.8 The BSQ showed a high validity that concurred with similar instruments, such as the corporal dissatisfaction subscale of the Eating Disorders Inventory (EDI).9 This questionnaire consisted of 34 items related to self image that are evaluated using a six-point frequency scale (1=never, 2=rarely, 3=sometimes, 4=often, 5=frequently, 6=always). Therefore, the range of scores is 34-204, threshold values of 105 or more being considered pathologic. The factors evaluated are: corporal dissatisfaction, fear of getting fat, feelings of low self-esteem due to appearance, and desire to lose weight. The control group was constituted by a total of 12 healthy women with no history of psychiatric or neurologic disease or of drug consumption. The mean age of the control group was 20 years (range 18-27 years). All study subjects, both patients and controls, were right-handed. The study was authorized by the hospital ethics committee. An informed consent form was signed by each study subject after receiving an explanation of the methodology to be used. Before performing scintigraphic scans, pregnancy was excluded by a specific test. SPECT procedure and quantitation
After the study subjects had rested for at least thirty minutes in a quiet room, a bolus of 99mTchexamethylpropyleneamine oxime, 99mTc-HMPAO (Ceretec®, Amersham Health), with an activity of 740 MBq, was injected through a cannula in antecubital vein, The radiopharmaceutical was prepared in strict accordance with the manufacturer’s instructions and administered within 15 minutes of preparation. Scan acquisition began within 30 minutes of injection. The scan was made with an Infinia Hawkeye® model (General Medical Electric Systems, Milwaukee, Wis) double-head scintigraph with an intrinsic spatial
Table 1. DISTRIBUTION OF THE SUBJECTS IN THE SAMPLE Ident.
Diag.
Age
BMI
BSQ
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
Control Control Control Control Control Control Control Control Control Control Control Control RA RA RA RA RA RA RA PB PB PB PB PB PB PB PB PB PB PB PB
23 19 19 21 28 19 21 19 19 19 21 19 24 20 18 26 23 37 24 28 31 19 24 24 35 36 18 43 32 24 30
24 20 19 22 19 23 21 24 22 23 20 21 21 19 15 17 19 18 18 19 29 19 29 20 28 22 20 23 22 20 22
44 40 68 62 37 43 48 75 88 86 38 60 80 74 90 71 159 96 118 183 111 73 191 181 148 136 164 177 86 177 114
Age, body mass index (BMI) and BSQ score (Body Shape Questionnaire) of the subjects in the sample. Diag: group diagnosis; RA: restrictive anorexia; PB: purgative bulimia.
resolution in the central field of vision (CFOV) of 3.8 mm FWHM (Full-Width Half-Maximum). Parallel, low-energy, high-resolution (LEHR) collimators were used. The acquisition matrix was 64x64, with a 1.0 zoom. The acquisition orbit was a 360º circle in which 60 images were acquired (30 per head), each lasting 30 seconds. “Step & shoot” acquisition was used. Under these conditions, a slice thickness of 8.84 mm was obtained. Scans were processed by filtered retroprojection using a Metz filter (FWHM: 1.9; order 4.6). Image reorientation was performed, obtaining images from slices parallel to the orbitomeatal axis and sagittal and coronal slices. The Segami Neuromatching quantitation program was used. This program yields regions of interest (ROIs) semiautomatically: on transaxial images, the outer and inner limits of cortical activity are delimited manually. After this operation is performed, the
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Poblete García VM et al. Assessment of cortical brain blood flood by brain perfusion SPECT in patients with a diagnosis of eating behavior disorders
Fig. 1.—Images of transaxial slices showing the cortical regions of interest (ROIs) obtained by the semiautomatic quantitation method. Semiquantitative indices of cortical activity in these ROIs were obtained, taking cerebellar activity as a reference.
program automatically divides the cerebral cortex into ROIs. This process was applied to 8 successive transaxial slices, including almost all of the cortical regions (Fig. 1). Once these segments were obtained, the activity of 10 cortical regions was calculated from the mean count per pixel of the ROIs corresponding to the upper and lower frontal, parietal, temporal and occipital cortices of the right and left hemispheres. Regular elliptical ROIs also were applied manually to both cerebellar hemispheres. The activities of each cerebral region and the cerebellar hemispheres were obtained as mean counts per pixel. The cerebellar count, consisting of the mean count per average pixel of each cerebellar hemisphere, was used as the reference activity. Later, semiquantitative indices of cerebral cortical activity and cerebellar activity were calculated using the formula [(mean count per pixel in cortical ROIs/mean count per average pixel of both cerebellar hemispheres) x 100]. These indices were evaluated and compared statistically between the control group and patients 14
with EBD, and between RA and PB patients in the EBD group. Statistical analysis
Data were analyzed using analysis of variance of a factor (ANOVA) to evaluate the differences in mean uptake between RA and PB groups in relation to normal subjects. The same method was used to evaluate the possible influence of drug treatment on cerebral perfusion in treated versus untreated patients and the difference between types of treatment in the group of treated patients. The statistical significance level was p<0.05.
RESULTS
Mean BMI values calculated in the patients were 18.14 in the RA group (range 15-21) and 22.75 in the PB group (range 19-29). In the control group, mean
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Poblete García VM et al. Assessment of cortical brain blood flood by brain perfusion SPECT in patients with a diagnosis of eating behavior disorders Table 2. DISTRIBUTION OF MEANS AND 95% CONFIDENCE INTERVALS OF THE CORTICAL ACTIVITY INDICES OBTAINED IN DIFFERENT CEREBRAL REGIONS ROI Right upper frontal
Control
RA
PB
110.1 (97.8-102.5)
94.4 (89.3-99.5)
93.06 (90.4-95.6)
Left upper frontal
91.5 (89.3-93.7)
88.1 (83.8-92.4)
86.40 (83.8-88.9)
Right lower frontal
99.0 (96.5-101.5)
94.8 (91.4-98.2)
95.30 (93.6-96.9)
Left lower frontal
90.8 (88.4-93.1)
88.2 (84.9-91.4)
89.30 (87.9-90.6)
Right parietal
91.2 (89.3-93.2)
87.0 (83.2-90.8)
86.10 (83.8-88.3)
Left parietal
82.1 (80.1-84.06)
76.4 (72.9-80)
77.20 (75.2-79.2)
Right temporal
93.6 (91.7-95.5)
88.4 (85.9-90.9)
89.50 (88.2-90.9)
Left temporal
83.1 (79.9-83.5)
78.2 (75.3-81.1)
81.70 (79.9-83.5)
Right occipital
93.7 (91.3-96.1)
89.7 (87-92.5)
91.10 (89.2-93.04)
Left occipital
88.9 (87.2-90.6)
85.0 (81.6-88.3)
88.20 (85.8-90.6)
In bold, the regions that showed statistically significant differences in patients versus control subjects. ROI: regions of interest; RA: restrictive anorexia; PB: purgative bulimia.
BMI was 21.5 (range 19-24). Mean BSQ score (Table 1) was 98.28 (range 71-159) in the RA group and 145.08 (range 73-191) in the PB group. In the group of control subjects, these values were 57.4 (range 3788). Cerebral cortical perfusion analyzed using the equation (right lobe activity/left lobe activity) x 100 disclosed more activity in the control group subjects in the right lobes than in the left lobes. The difference was more marked in the temporal lobes, with 11% more activity in the right lobes than in the left, and less marked in the occipital lobes, where the difference was only 5%. In the EBD patient group, comparison of the mean activity of each cortical region to the control group showed lower values in both RA and PB patients in all of the cortical regions studied. Statistical analysis of these differences revealed that they were statistically significant in the left parietal (p=0.020), right temporal (p=0.004) and left temporal lobes (p=0.015) of the RA group and in the right upper frontal (p<0.001), left upper frontal (p=0.008), right lower frontal (p=0.042), right parietal (p=0.002), left parietal (p=0.002), and right temporal (p=0.002) of the PB group. The 95% confidence intervals of the mean uptakes in each cerebral region of the three study groups are shown in Table 2. With respect to medication, there was no difference in the distribution of cerebral blood flow between medicated and nonmedicated patients. In the medicated patients there were no differences between those treated
with antidepressants alone and those treated with a combination of antidepressants and benzodiazepines (ANOVA: p>0.05).
DISCUSSION
In cerebral perfusion studies it is important to know the normal pattern of distribution of a radiopharmaceutical to evaluate significant alterations in any neuropsychiatric condition. In this sense, many studies report an asymmetrical radioisotope distribution with predominance of the right hemisphere over the left hemisphere.10-13 In addition, this asymmetry has been observed to increase with age, the greatest difference between right and left side being found in subjects age 60 to 70 years.14 The results of our control group subjects coincide with these studies because we found more perfusion in all of the regions of the right hemisphere compared to the left hemisphere, particularly in the temporal lobes. EBDs are complex processes in which biological, emotional and behavioral components converge in the pathophysiology. These patients commonly suffer other disorders, such as major depression15,16 or obsessive-compulsive disease traits.17 Nonetheless, the pathogenesis of these conditions is still unknown. There is evidence of a neuronal disorder in these conditions because the clinical syndrome can be reproduced by injury to the right lower prefrontal cortex.18,19 The fact that perinatal complications are associated with the development of these conditions
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Poblete García VM et al. Assessment of cortical brain blood flood by brain perfusion SPECT in patients with a diagnosis of eating behavior disorders
also is suggestive of an organic cerebral substrate.20 In addition, the findings obtained with neuropsychologic, electrophysiologic and neuropharmacologic techniques and functional and structural neuroimaging suggest the existence of an underlying neural disorder21. Kornreich et al.22 reported an increase in the size of the cerebral ventricles in AN-diagnosed adolescent children compared with healthy controls, but the difference did not reach statistical significance. Husain et al.23 found a significantly smaller thalamus and middle cerebral regions in patients with anorexia compared to control subjects and to patients with bulimia. The comparison of mean cortical activity values in our study showed that mean cortical activity in these patients, both the RA and PB subgroups, is lower in all cortical regions. Similar findings have been reported in earlier studies, such as that of Delvenne et al.24 with PET, in which overall cerebral hypometabolism was reported. However, this hypoperfusion was only statistically significant in some regions, these differences being related to the type of eating disorder the patients had: in patients with RA, statistically significant hypoperfusion was seen in both temporal lobes and the left parietal lobe, whereas in patients with PB we found a more generalized and significant involvement, with hypoperfusion in bilateral parietal lobes, the right temporal and upper frontal and right lower frontal cortex. These findings concur in part with those obtained by the Delvenne group, discussed previously, because the hypometabolism described in patients with AN predominated in the parietal and frontal regions, which was not found in our study group. More recently, the same group described hypometabolism in the parietal regions of patients with AN as well as BN criteria,25 which does agree with our findings. Our results also show certain similarities with those of other studies. For instance, Gordon et al.26 observe marked asymmetry between the temporal lobes in 13 of 15 patients with AN, 8 with left-sided and 5 with right-sided hypoperfusion. These findings persisted in 3 of the patients in which the study was repeated after weight was restored. This fact suggests the existence of an underlying organic condition. However, this group found no disturbance in the parietal regions, in contrast with our findings. In a group of 21 patients with AN (19 women and 2 men) of an age similar to the women in our sample, in which 19 had recovered their weight, Rastam et al.27 evaluated cerebral cortical blood flow by 99mTc16
HMPAO SPECT. They observed hypoperfusion of the temporoparietal regions and orbitofrontal cortex long after normal weight was regained. Although there is no clear explanation for this temporoparietal affectation, given the similarity with the findings described in these studies, these alterations seem to be a consequence of neurophysiologic or morphologic aspects of ED.28 Impaired frontal perfusion in patients with AN has been reported by other groups, such as Takano et al.29 and Naruo et al.30, who found diminished perfusion of the anterior cingulate gyrus circumvolution of bilateral nature in patients with RA. These authors claim that these findings suggest that hypoperfusion of the frontal cortex, which includes the anterior cingulate gyrus, could be associated with both the implacable desire that these patients have to be thin and their altered perception of their body image. This claim could explain why we did not encounter significant hypoperfusion of the frontal cortex in the group of patients diagnosed as RA, whereas this finding was present in patients with PB, since the group of bulimic women showed clearly abnormal BSQ scores (>105), which was indicative of more corporal dissatisfaction, whereas the group of anorexic women, which were the majority, presented scores below the limit of pathology. These data may be suggestive of a certain relation between frontal hypoperfusion and corporal dissatisfaction, fear of gaining weight and a wish to lose weight in bulimic patients, a finding not seen in patients with RA. With regard to frontal perfusion abnormalities, Nozoe et al.,31 in a study of patients with AN and BN, obtained results that were the opposite of those seen in our study because they demonstrated increased perfusion of inferior frontal regions in patients with BN compared to both the AN group and control group. In the same group, when the perfusion study was repeated after food intake, it showed increased perfusion in the upper and lower frontal regions of patients with AN, but no changes in the patients with BN. One possible explanation for this finding would be the relation between the frontal cortex, hypothalamus, and appetite control mechanisms.32 Absence of change in the lower frontal areas in patients with BN after intake could be related to a deficient function of the satiety mechanism, which would be secondary to hyperphagia in these patients. For example, it has been reported that frontal lobe lesions produce secondary hyperphagia.33 In contrast, the increase in frontal
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Poblete García VM et al. Assessment of cortical brain blood flood by brain perfusion SPECT in patients with a diagnosis of eating behavior disorders
perfusion after intake in patients with AN is related to an overactive system of satiety control. This explains the hypophagia typical of these patients. In relation to our findings, the hypoperfusion demonstrated in frontal regions in our patients with BN could be related to this hypothetical deficiency in satiety system function, although it is impossible to draw conclusions in light of the nonspecificity and incongruence of the findings and the small number of patients studied. It is interesting to emphasize that most semiquantitative studies of cerebral cortical perfusion in patients with EBD use cerebellar activity as a reference because the alterations produced by these conditions affect the cerebral cortex exclusively.34 However, Addolorato et al.35 encountered diminished cortical perfusion of the temporo-parieto-occipital regions of an asymmetrical nature in a young woman diagnosed as AN. In addition, there is an important decrease in the perfusion of the left cerebellar hemisphere, which was visualized as smaller than the opposite cerebellar hemisphere. Computed tomography (CT) showed increased external cerebrospinal spaces, asymmetrical cerebral atrophy without focal parenchymal lesions, and marked cerebellar atrophy. These findings suggest that cerebellar alterations can be found in patients with certain forms of AN, although this was not so in our case because all the subjects in our sample showed sustained, symmetrical uptake by the cerebellar hemispheres, thus validating the use of this activity as a reference in the calculation of semiquantitative indices of cerebral cortical activity. We cannot discuss CT findings because this study was not performed in any participants, whether control subjects or patients. CT is performed only in patients in whom the symptoms suggest organic neurologic damage, which did not occur in any of our patients. The limitations of our study were, on the one hand, the inclusion of patients with pharmacologic treatment in our sample, which could have affected the results. However, we found no statistically significant differences between treated and untreated patients and between treated patients who took one type of medication or another. On the other hand, the small number of subjects in our sample precludes definitive conclusions, although other study samples in the bibliography had results similar to ours. In conclusion, patients with ED, whether RA or PB, showed a pattern of overall cerebral hypoperfusion compared to the control group. This hypoperfusion was more significant in the temporoparietal regions,
although there was more temporal lobe affectation in the case of patients with RA and more parietal affectation in PB. These findings could be considered a specific biological marker in these patients because they were seen in patients with different degrees of evolution of their symptoms. Nevertheless, the frontal cortical hypoperfusion that was demonstrated exclusively in patients with PB could be related more with the patient’s degree of dissatisfaction with body image, which was clearly changed in patients with PB but not in patients with RA.
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