Yoshiaki Nakabeppu

Comparison of regional cerebral blood flow in patients with anorexia nervosa before and after weight gain.

We investigated changes in regional cerebral blood flow (rCBF) before and after weight gain in patients with restrictive anorexia nervosa (AN-R) in comparison with findings in normal subjects. We assessed resting rCBF using single photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime in 12 AN-R patients and 11 controls. Each patient was examined at two time points, at the beginning of treatment and after weight gain (average examination interval=88+/-26 days). Control subjects were examined only once. Before treatment, the AN-R group had lower rCBF in the bilateral anterior lobes, including the anterior cingulate cortex (ACC), and in the right parietal lobe, the insula, and the occipital lobes. After weight gain, the patients showed significant increases in the right parietal lobe and decreases in the basal ganglia and cerebellum in accordance with significant improvement in body weight and eating attitudes. However, they showed persistent decreases in the ACC area even after weight gain compared with findings in the controls. A significant positive correlation was observed between body mass index and rCBF in the occipital lobes in the patients. These results suggest that weight gain is associated with a normalization of rCBF in a number of brain areas, but that the low level of rCBF in the ACC at baseline is unaffected by treatment in AN-R.

Comparison of regional cerebral blood flow in patients with eating disorders

We used single photon emission computed tomography (SPECT) with Tc-99m-HMPAO to examine the characteristics of regional cerebral blood flow (rCBF) in five patients with bulimia nervosa (BN), eight patients with anorexia nervosa (AN), and in nine healthy controls. The SPECT examinations were performed before and after food intake stimulus, and the values of the corrected ratio (R) for rCBF in 10 cerebral cortical regions before (Rbefore) and after eating (Rafter) were calculated. The asymmetry indices (AI) of the R values for the left and right side of each cortical region and the percent change from Rbefore to Rafter (%change) were computed. In comparison with the other two groups, BN patients showed significantly higher Rbefore values in the bilateral inferior frontal and left temporal regions. The AN patients showed significantly lower Rbefore values in the left parietal region than the control group. There were no significant differences in Rafter values among the three groups. The %change values in the AN group showed the greatest increase in 9 out of the 10 regions. In contrast to the positive values obtained from the 10 regions observed in the AN group, 5 out of the 10 regions in the BN group showed negative values. Among the three groups, significant differences in %change were observed on both sides of the inferior frontal, temporal, parietal, and occipital regions. These findings indicate that differences in cerebral function of BN and AN patients can be characterized through SPECT imaging.

Decreases in blood perfusion of the anterior cingulate gyri in Anorexia Nervosa Restricters assessed by SPECT image analysis.

BackgroundIt is possible that psychopathological differences exist between the restricting and bulimic forms of anorexia nervosa. We investigated localized differences of brain blood flow of anorexia nervosa patients using SPECT image analysis with statistic parametric mapping (SPM) in an attempt to link brain blood flow patterns to neurophysiologic characteristics.MethodsThe subjects enrolled in this study included the following three groups: pure restrictor anorexics (AN-R), anorexic bulimics (AN-BP), and healthy volunteers (HV). All images were transformed into the standard anatomical space of the stereotactic brain atlas, then smoothed. After statistical analysis of each brain image, the relationships among images were evaluated.ResultsSPM analysis of the SPECT images revealed that the blood flow of frontal area mainly containing bilateral anterior cingulate gyri (ACC) was significantly decreased in the AN-R group compared to the AN-BP and HV groups.ConclusionsThese findings suggest that some localized functions ofthe ACCare possibly relevant to the psychopathological aspects of AN-R.

Aberrant brain activation following motor skill learning in schizophrenic patients as shown by functional magnetic resonance imaging.

BACKGROUND Motor skill learning may be impaired in schizophrenia. While functional brain imaging studies have shown reduced activation during motor task performance in schizophrenic patients, brain activity changes with motor skill learning in these patients have not been studied by functional imaging. METHODS A sequential complex motor task involving the right hand was performed by nine medicated schizophrenic patients and 10 age-matched healthy controls. Functional magnetic resonance images were obtained using a gradient echo, echoplanar imaging (EPI) pulse sequence before and after 1 week of training in performing the task. RESULTS Bilaterally, patients showed significantly less blood oxygenation level-dependent (BOLD) signal response in the premotor area (PMA) before beginning motor training than controls. BOLD signal response increased in the left PMA of schizophrenic patients after 1 week of motor training; in contrast, the signal decreased in the left PMA of control subjects. Training effects concerning the number of finger movement sequences achieved did not differ between groups. Daily neuroleptic dose did not significantly affect changes with training in BOLD signal response in the PMA. CONCLUSIONS These preliminary results suggest that schizophrenic patients have dysfunction of neural networks in areas including the PMA that are involved in executing a complex motor task. In terms of brain activity, motor learning may be less efficient or slower in the patients than in healthy subjects.

Clinical and molecular genetic assessment of a chorea-acanthocytosis pedigree

BACKGROUND Chorea-acanthocytosis (ChAc) is an autosomal recessive hereditary disease characterized by neurodegeneration in the striatum and acanthocytosis that is caused by mutations in the VPS13A gene. There are only few reports that studied clinical status of the obligate carriers of ChAc. Clinical courses with follow-up neuroradiological and neuropsychological evaluations in individuals with ChAc have been rarely reported. METHODS We followed an index patient with ChAc and evaluated the clinical features of the pedigree members. Genetic analyses of VPS13A and genes responsible for other neuroacanthocytotic and neurodegenerative diseases were performed. CONCLUSIONS The index patient was homozygous for a 3889C>T nonsense mutation in the VPS13A gene and presented with a typical ChAc phenotype. Neuropsychological evaluation with brain imaging in the patient over 3 years revealed atrophy and a decrease in blood flow at the basal ganglia and frontal lobe, and impairment in cognitive function reflecting frontal lobe dysfunction in progressive manners. Four out of five heterozygous mutation carriers in the pedigree showed signs or symptoms potentially attributable to a heterozygous VPS13A mutation.

Decreased perfusion of the bilateral thalami in patients with chronic pain detected by Tc-99m-ECD SPECT with statistical parametric mapping.

The purpose of this study was to examine whether the Tc-99m-ECD SPECT can detect any difference between the brain perfusion in patients with chronic pain and normal controls by means of the Statistical Parametric Mapping (SPM96). The subjects were twelve patients with chronic pain (CP group) and twelve normal controls (NC group). After informed consent was obtained, 720 MBq of Tc-99m-ECD was intravenously injected as a bolus. The SPECT data were acquired once for 20 mins from 5 mins after i.v. injection of Tc-99m-ECD, with a triple-head rotating gamma camera. The SPECT data were transformed into a standard stereotactic space, and group comparisons between CP and NC groups were performed on a voxel-by-voxel basis. The subset of voxels exceeding a threshold of p<0.001 in omnibus comparisons and remaining significant after correction for multiple comparison (p<0.05) was displayed as a volume image rendered in three orthogonal projections. There was a significant decrease in perfusion in the bilateral thalami in the CP group, suggesting that perfusion in the thalamus generally decreases in patients with chronic pain. Tc-99m-ECD SPECT with SPM96 may be useful for studies of the mechanisms of chronic pain.

The role of adrenocortical scintigraphy in the evaluation of unilateral incidentally discovered adrenal and juxtaadrenal masses.

We reviewed the findings of adrenocortical scintigraphy with131I-6-beta-iodomethyl-19-norcholesterol (NCL-6-131I) of 39 patients to clarify its role in the evaluation of unilateral adrenal or juxtaadrenal masses incidentally discovered by CT, ultrasonography or plain radiography. Twenty-seven benign adrenal masses showed various scintigraphic findings (hot nodule: 12 silent adenomas, warm nodule: one solid mass, normal appearance: one cyst and 2 solid masses, diffuse decrease: each one; solid mass, myelolipoma, ganglioneuroma and calcified adrenal and partial or complete defect: each one; solid mass, myelolipoma and ganglioneuroma and 2 cysts and 2 pheochromocytomas); while a partial or complete defect was shown in a nonfunctioning carcinoma and 3 metastases and a complete defect or inhomogeneous uptake without opposite adrenal visualization was shown in 2 patients with cortisol-producing carcinoma. Therefore a hot nodule and an inhomogenous uptake or complete defect with nonvisualization of the opposite adrenal are specific to a benign tumor and a cortisol-producing carcinoma, respectively. The impaired tumor uptake of NCL-6-131I is a nonspecific finding. The scintigraphic findings of juxtaadrenal masses were normal in 4 and deviated adrenals in 2. Thus adrenocortical scintigraphy can identify silent adenomas and cortisol-producing carcinomas among the adrenal masses and may help to differentiate juxtaadrenal from adrenal masses.

Metastatic pulmonary pheochromocytomas : Positive I-123 MIBG SPECT with negative I-131 MIBG and equivocal I-123 MIBG planar imaging

Pulmonary metastases from malignant pheochromocytoma were seen with I-123 MIBG SPECT in a 16-year-old girl but were not visualized with I-123 MIBG planar imaging. She had a left adrenalectomy for a pheochromocytoma 7 years earlier. Two small pulmonary nodules were seen on chest X-ray and CT scans.

Radionuclide therapy of malignant pheochromocytoma with131I-MIBG

Three patients with malignant pheochromocytoma were treated with intravenous infusion of131I-MIBG. The dose per therapy ranged from 2.33 to 4.03 GBq. The repeated therapies were performed at intervals of 6, 11, 10 and 13 months in the first patient, 17 and 11 months in the second patient and 9 months in the third patient. Lumbago disappeared but little objective improvement was achieved in the first patient. The second patient exhibited a gradual decrease in catecholamine values with no change in tumor size. Remarkable decreases in tumor size and catecholamine values were observed in the third patient. No side effect was observed in any patient. The radiation dose absorbed by the main tumor was the highest at the first therapy and decreased with the number of therapies: 42, 26, 19, x and 9.0 Gy in the first patient, 63, 20 and 8.8 Gy in the second patient, and 81 and 40 Gy in the third patient. This was due mainly to the decrease in % uptake by the tumor of the131I-MIBG dose administered. Therefore the increase in the dose of131I-MIBG administered at the first therapy and/or shorter interval therapies seems to be important to obtain more therapeutic effects on malignant pheochromocytoma.

Three basic patterns of changes in serum thyroid hormone levels in Graves’ disease during the one-year period after radioiodine therapy

The purpose of this study was to clarify the characteristic patterns of the thyroid hormonal changes in Graves’ disease during the one-year period after131I therapy considering that few serial hormonal data during this period are available in the literature.MethodsThe levels of serum T3, T4 and FT4 before and during one year were plotted as a function of time in 70 therapy courses of 58 patients without subsequent antithyroid or steroid therapy.Results35 euthyroid, 6 hypothyroid and 29 hyperthyroid states were obtained during one year after therapy. Although individual patients had individual hormonal changing patterns, 3 common basic patterns were observed from baseline to one month (early) and thereafter (late), respectively. The early patterns were a decrease in 54 (77%), a minimum change in 8 (11.5%) and an increase in 8 (11.5%). The late patterns were a stable state after an initial decrease with a bottom followed by an increase (valley pattern) in 47 (67%), a stable state after an initial increase with a peak followed by a decrease with a bottom and a subsequent re-increase (mountain pattern) in 12 (17%) and a late stable state after a gradual slow decrease without an obvious bottom near or till one year (downhill pattern) in 11 (16%). The bottom level and the degree of hormonal recovery from the bottom determined the stable euthyroid, hypothyroid or hyperthyroid state in 49 (86%) of 57 with the valley or mountain pattern. Most of the bottom levels (81%) and transient abnormal changes including transient hypothyroidism (93%, 13/14), peak or hyperthyroidism (85%, 11/13) and euthyroidism (67%, 10/15) appeared within 6 months. The post-therapeutic stable euthyroid, hypothyroid or hyperthyroid state could be judged from the hormonal patterns in 57% (39/68) from 2.5 to 6 months, in 18% (12/68) from 6 to 9 months and in 25% (17/ 68) thereafter.ConclusionAlthough the changes in thyroid hormones are not constant in Graves’ disease during one year after131I therapy, there are three basic patterns; valley, mountain and downhill patterns from one month after therapy. The post-therapeutic stable state can be judged by the hormonal level recovered from the bottom in most patients.