Bilge Volkan-Salanci

The effect of clozapine on regional cerebral blood flow and brain metabolite ratios in schizophrenia: Relationship with treatment response

The purpose of this study was to investigate the effect of clozapine on regional cerebral blood flow (rCBF) and its relationship with response to treatment. In addition, we aimed to study the influence of clozapine on proton magnetic resonance spectroscopy ((1)H-MRS) findings in the dorsolateral prefrontal cortex (DLPFC) in a subgroup of patients. Psychopathology, neurocognitive functioning, and SPECT imaging of 22 patients were assessed at the baseline and 8 weeks after the initiation of clozapine treatment. In 10 of these patients intermediate-echo (TE: 135 ms) single-voxel (1)H-MRS was also performed at the baseline and after 8 weeks. Clozapine treatment increased the right frontal (superior and medial)/caudate perfusion ratio in the whole group, while it increased bilateral frontal (superior and medial)/caudate perfusion ratios in treatment responders. In addition, percentage changes in left and right frontal (superior and medial)/caudate perfusion ratios compared to the baseline were higher in treatment responders than in non-responders. The improvement in attention was related to the increase in percentage change in the right frontal (superior and medial)/caudate perfusion ratio, while the improvement in verbal fluency was related to the increase in percentage changes in both right and left frontal (superior and medial)/caudate perfusion ratios and to right frontal (superior and medial)/thalamus perfusion. Baseline frontal (superior and medial)/thalamus perfusion could explain 32% of the variability of percentage improvements in psychopathology. (1)H-MRS showed that the baseline PANSS general psychopathology score was inversely correlated with the baseline NAA/Cre ratio. An increased NAA/Cre ratio in DLPFC after 8 weeks of clozapine treatment was also revealed by (1)H-MRS. Our SPECT imaging results suggest the presence of an imbalance in fronto-striato-thalamic circuitry that changes with clozapine, especially in the responders, while (1)H-MRS results indicate a supportive effect of clozapine on neuronal integrity.

Thyroid cancer in pediatric age group: an institutional experience and review of the literature.

Very few have been reported on children with differentiated thyroid cancer (DTC), although 15% of them are diagnosed below 20 years of age. Children with DTC present with more advanced disease; however, they have a more favorable outcome. In this paper, we aimed to present the data in our institution on pediatric DTC patients, making an emphasis on the risk factors of metastasis and recurrence, as well as to the outcome of treatment. Clinical data of 50 pediatric patients referred to our institution for radioiodine treatment (RAI) between 1976 and 2010 were obtained. Papillary carcinoma was the most common histopathologic diagnosis (36 patients) followed by papillary carcinoma with follicular variant (10 patients). Multifocality was reported in 66% of the pathology reports. At the time of diagnosis 35 patients had regional lymph node metastasis, 18 had local invasion, and 11 had distant metastasis. No distant metastasis was present in patients with unifocal disease (P=0.018). The mean duration of follow-up was 77.6±62.7 months. Patients with local disease had longer disease-free survival than patients with distant metastasis (P=0.033). Despite the small number of patients, the follow-up was relatively long and the presented results confirmed overall good prognosis in children with DTC.

Etiological yield of SNP microarrays in idiopathic intellectual disability.

Intellectual disability (ID) has a prevalence of 3% and is classified according to its severity. An underlying etiology cannot be determined in 75-80% in mild ID, and in 20-50% of severe ID. After it has been shown that copy number variations involving short DNA segments may cause ID, genome-wide SNP microarrays are being used as a tool for detecting submicroscopic copy number changes and uniparental disomy. This study was performed to investigate the presence of copy number changes in patients with ID of unidentified etiology. Affymetrix(®) 6.0 SNP microarray platform was used for analysis of 100 patients and their healthy parents, and data were evaluated using various databases and literature. Etiological diagnoses were made in 12 patients (12%). Homozygous deletion in NRXN1 gene and duplication in IL1RAPL1 gene were detected for the first time. Two separate patients had deletions in FOXP2 and UBE2A genes, respectively, for which only few patients have recently been reported. Interstitial and subtelomeric copy number changes were described in 6 patients, in whom routine cytogenetic tools revealed normal results. In one patient uniparental disomy type of Angelman syndrome was diagnosed. SNP microarrays constitute a screening test able to detect very small genomic changes, with a high etiological yield even in patients already evaluated using traditional cytogenetic tools, offer analysis for uniparental disomy and homozygosity, and thereby are helpful in finding novel disease-causing genes: for these reasons they should be considered as a first-tier genetic screening test in the evaluation of patients with ID and autism.

The role of brain perfusion SPECT in moyamoya disease

Moyamoya disease (MMD) is a cerebrovascular disorder involving stenosis of brain vessels. Brain perfusion SPECT in MMD demonstrates impaired perfusion in ischemic areas. We present a 6-year-old boy with MMD. The patient had numbness on the right arm and simultaneous electroencephalography changes while studying arms up on the table. To differentiate seizure and ischemic symptoms, brain perfusion SPECT studies were obtained when the patient was asymptomatic (SPECT-A) and during the symptoms-EEG changes (SPECT-B). SPECT-A showed perfusion defect on the right frontal cortex, hypoperfusion on the right parieto-occipital region and slightly increased perfusion on the left parietal cortex. SPECT-B displayed significant hyperperfusion on the left parietal cortex; hypoperfusion on the right parietal, right temporal, right parieto-occipital and left frontal cortex. Additionally, brain perfusion SPECT of the childs younger brother diagnosed with MMD showed decreased regional cerebral perfusion. Physiopathological mechanisms of our patients SPECT findings and indications of brain perfusion SPECT in MMD were also discussed.

A new autosomal dominant Peters’ anomaly phenotype expanding the anterior segment dysgenesis spectrum

Purpose:  To test the association of genes involved in anterior segment development in a family with autosomal dominantly inherited Peters’ anomaly (PA) with a unique ocular phenotype.

Nuclear Medicine in Thyroid Diseases in Pediatric and Adolescent Patients.

Both benign and malignant diseases of the thyroid are rare in the pediatric and adolescent population, except congenital hypothyroidism. Nuclear medicine plays a major role, both in the diagnosis and therapy of thyroid pathologies. Use of radioactivity in pediatric population is strictly controlled due to possible side effects such as secondary cancers; therefore, management of pediatric patients requires detailed literature knowledge. This article aims to overview current algorithms in the management of thyroid diseases and use of radionuclide therapy in pediatric and adolescent population.

Neurochemical evaluation of brain function with 1H magnetic resonance spectroscopy in patients with fragile X syndrome.

Fragile X syndrome (FXS) is the most common hereditary disorder of intellectual disability. Cognitive deficits involve executive function, attention, learning and memory. Advanced neuroimaging techniques are available, and 1H magnetic resonance spectroscopy (MRS) can be used as a complementary method to MR imaging to understand disease processes in brain, by in vivo demonstration of brain metabolites. MRS was performed in 13 male patients with FXS full mutation, and 13 age‐ and sex‐matched healthy controls. FXS diagnosis was based on clinical evaluation, followed by detection of FMR1 full mutation. Axial T2 TSE, sagittal T1 SE and coronal 3D MPRAGE images were obtained for both morphological imaging and voxel localization. Following evaluation of conventional images, multivoxel MRS (CSI) through supraventricular white matter and single voxel MRS (svs) with an intermediate echo time (TE:135 ms) from the cerebellar vermis were performed. Choline/Creatine (Cho/Cr), N‐acetyl aspartate/Creatine (NAA/Cr), and Choline/N‐acetyl aspartate (Cho/NAA) ratios were examined at right frontal (RF), left frontal (LF), right parietal (RP), left parietal (LP), and cerebellar vermian (C) white matter. Statistical analyses were done using t‐test and Mann–Whitney U tests. A statistically significant difference was observed in RP Cho/NAA ratio (cell membrane marker/neuroaxonal marker), FXS patients having lower levels than controls (P = 0.016). The results should be evaluated cautiously in parallel to consequences in brain metabolism leading to alterations in neurotransmitter levels, osmoregulation, energy metabolism and oxidative stress response described in animal models. MRS may serve to define a metabolic signature and biomarkers associated with FXS.

The Relation Between Perfusion Pattern of Hepatic Artery Perfusion Scintigraphy and Response to Y-90 Microsphere Therapy

Objective: Hepatic artery perfusion scintigraphy is a routine procedure for patient evaluation before Y-90 radiomicrosphere therapy and mostly used for prediction of extrahepatic leakage. Moreover, it also displays perfusion pattern of tumours, which is an important parameter on success of the therapy. The aim of this study is to assess the relation between the perfusion pattern on hepatic artery perfusion scintigraphy and radiomicrosphere therapy response. Methods: A total of 99 radiomicrosphere therapy applications were carried out in 80 patients (M/F: 55/25). Results: Heterogeneous and diffuse perfusion patterns were observed in 47 patients and 52 patients, respectively. The patients with diffuse perfusion pattern had better therapy response both on FDG PET/CT (p= 0.04) and CT (p=0.008) when compared to those with heterogenous perfusion pattern. Conclusion: Perfusion pattern observed on hepatic artery perfusion scintigraphy may be a successful predictor of early response to radiomicrosphere therapy. Conflict of interest:None declared.