Tc-HMPAO Brain Perfusion Single-Photon Emission Computed Tomography in Children with Down Syndrome: Relationship to Epilepsy, Thyroid Functions, and Congenital Heart Disease

In recent years, it has been possible for patients with Down syndrome to live longer with advanced medical treatment and social support. As a result, the problems of these patients, such as thyroid diseases, leukemia, and Alzheimer disease, would be encountered more frequently. In this study, we aimed to perform the brain perfusion of children with Down syndrome by technetium 99m hexamethylpropylene amine oxime (Tc-HMPAO) single-photon emission computed tomography (SPECT) and to determine the relationship between brain perfusion and epilepsy, thyroid function tests, congenital heart disease, and level of mental and motor development. Thirty patients with Down syndrome, aged between 1 and 15 years, were included in our study. Demographic data, the existence of epilepsy and congenital heart defects, the level of mental and motor development, serum levels of thyroid hormones, and autoantibodies were determined. All patients underwent computed tomography (CT) and/or magnetic resonance imaging (MRI). Cerebral SPECT was performed in all cases to evaluate the brain perfusion pattern. According to the visual evaluation of cerebral SPECT results, hypoperfusion was detected in 11 cases (37%). Patients with cerebral hypoperfusion (group 1) and patients with normal cerebral perfusion (group 2) were compared. There was no difference between group 1 and group 2 in terms of demographic data, congenital heart defects, IQ levels, thyroid hormones, and autoantibodies, but the incidence of epilepsy was significantly higher in group 1 (P , .001). When motor and mental development levels were compared, it was found that cases in group 1 were significantly more retarded in personal-social and fine motor skills (P , .05). The present study showed that cerebral hypoperfusion in children with Down syndrome is mostly related to epilepsy and the other coexisting conditions, congenital heart disease and hypothyroidism. Patients with cerebral hypoperfusion also have more retarded developmental levels, especially in personal-social and fine motor skills. (J Child Neurol 2006;21:610–614; DOI 10.2310/7010.2006.00144). Down syndrome is characterized by the typical dysmorphic appearance and moderate mental retardation, in addition to a variety of abnormalities involving multiple organ systems. Congenital heart diseases, hypothyroidism, gastrointestinal malformation, immune system defects, leukemia, and Alzheimer disease–type dementia after the age of 35 years are common in Down syndrome. In adult patients with Down syndrome with Alzheimer disease, bilateral brain hypoperfusion was detected by single-photon emission computed tomography (SPECT) studies. Similar perfusion defects have also been demonstrated in children with Down syndrome. The aim of this study was to investigate changes in brain perfusion using technetium 99m hexamethylpropylene amine oxime (TcHMPAO) SPECT in children with Down syndrome and to determine the relationship between cerebral hypoperfusion and hypothyroidism, congenital heart disease, epilepsy, and the level of mental and motor development. Material and Methods Thirty children with Down syndrome (18 boys, 12 girls), aged 1 to 15 years, were included in this study. The patients, all with regular trisomy, had no history of birth asphyxia. Informed consent was obtained from parents for this investigation, and the Faculty Ethics Committee approved the study. Data relating to age, sex, weight, height, head circumference, the existence of epilepsy or congenital heart disease, and the level of mental and motor development were recorded. If epilepsy was present, it was defined as the occurrence of at least two unprovoked seizures in at least 24 hours. Serum free triiodothyronine, free thyroxine, thyroidstimulating hormone, and antithyroid peroxidase antibody and antithyroglobulin antibody levels were determined by chemical immunoassay methods (Immulite Diagnostic Products Corporation, Los Angeles, CA). In all patients, computed tomography (CT) and/or magnetic resonance imaging (MRI) performed within 1 week from the SPECT examination did not show focal brain abnormalities, the only pathologic finding being common ischemic changes of the brain in one patient (patient 7). To identify the mental and intellectual capacity of the patients, the Denver Developmental Screening Test was performed in children under 6 years of age. The personal-social, fine motor adaptive, language, and gross motor functions were evaluated with the Denver Developmental Screening Test. The Denver Developmental Screening Test results are given in terms of the number of parameters that resulted in failure and the percentage of failures according to age group. IQ scores were performed for patients older than 6 years. SPECT Study Before the SPECT study was performed, the patients were placed in a quiet environment, an intravenous line was inserted, and 0.5 mCi/kg (18.5 MBq/kg) of Tc-HMPAO (maximum 15 mCi) was administered a few minutes later. SPECT was performed within 60 to 90 minutes after intravenous administration of the radiotracer. Either the head or the whole trunk was placed in a polystyrene vacuum cushion, depending on the size of the patient. The acquisition was performed under monitored sedation administered following injection of the tracer. A rotating, large–field of view gamma camera interfaced to a dedicated computer system (Philips Diagnost Tomo, Philips, Eindhoven, the Netherlands) was used. During a 360-degree rotation, a low-energy, high-resolution collimator acquired 64 images with a 128 3 128 matrix. Transaxial slices were obtained parallel to the anterior commissureposterior commissure line. These slices displayed cerebellar, cerebral cortical, and subcortical lobes. Transaxial, coronal, and sagittal slices were analyzed visually. Visual Evaluation Interpretation of the SPECT scans was performed qualitatively by reviewing the images on a computer screen and by one experienced physician who was blind to the clinical, electroencephalographic, and structural imaging data. A region was interpreted to show decreased perfusion if the degree of uptake appeared to be substantially lower than that of adjacent and contralateral areas of the brain. Statistical Analysis According to visual analysis, patients were classified as group 1 (patients with hypoperfusion on brain perfusion SPECT) and group 2 (patients with normal brain perfusion SPECT). The existence of thyroid dysfunction, epilepsy, congenital heart defects, and mental and motor deficit was compared between the groups. The Mann-Whitney U-test was used to compare the parameters. The results were expressed as mean 6 standard 610 Journal of Child Neurology / Volume 21, Number 7, July 2006