Quantitative measurement of iron in NBIA patients with quantitative susceptibility mapping and clinical evaluation

Presentation of the Thesis: Özge Uygun Yıldıran, Quantitative Measurement of Iron in NBIA patients with Quantitative Susceptibility Mapping and Clinical Evaluation, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Thesis in Neurology, Istanbul, 2020. Introduction: Neurodegeneration with brain iron accumulation (NBIA) is a rare and heterogeneous group of disorders characterized by progressive motor dysfunction, cognitive impairment, epilepsy, ocular findings as well as radiologic and pathologic evidence of excessive iron accumulation in brain, particularly in the basal ganglia (BG). The aim of this study is to demonstrate and measure quantity of iron in BG with a new sensitive method and compare it among BG nucleus. As well as, it is aimed to show the correlation between amount of iron accumulation and the clinical course of disease, disease subtypes, age of onset. Methods: In this study, patients genetically diagnosed with NBIA (n = 16, 9 PKAN, 3 MPAN, 2 PLAN, 2 Kufor Rakeb disease), age and gender compatible 11 healthy control group were investigated in Istanbul University, Istanbul Faculty of Medicine, Department of Neurology, Department of Child and Adolescent Neurology. Three Tesla Magnetic Resonance (MR) images were performed, T1, T2 images, susceptibility-weighted imaging (SWI) studies were obtained. Based on SWI imaging, the amount of quantitative iron in BG nuclei (GP, CN, SN, thalamus, NR and putamen) was evaluated by the QSM method and the results were given in parts per million (ppm). Also, Burke Fahn Marsden dystonia scale was used to determine the clinical weight. The measured parameters were compared between the patient and control groups by using the SPSS (Statistical Package for the Social Sciences) program. Results: There was approximately more than 2 times iron accumulation in the GP in NBIA patients. In contrast, the amount of iron in putamen was 2.5 times higher in healthy controls compared to NBIA patients. While the disease subgroups and healthy controls were compared, the amount of iron in GP of patients with PKAN was found 2.5 times higher than healthy controls. On the other hand, more iron accumulation was revealed in CN in healthy controls. When PKAN patients with compound heterozygous and homozygous mutations compared, more than 4 times iron was detected in CN of patients with compound heterozygous mutation. While classic and atypical PKAN patients were compared, iron was 2.5 times higher in SN in atypical patients. In MPAN patients, iron amount was 2.5 times higher in GP and SN compared to healthy controls. When PKAN and MPAN patients were evaluated among themselves, no significant difference was observed in terms of iron accumulation. There was no correlation between iron accumulation and age of onset, clinical weight (BFMS), sex, and subtypes of disease. Since the number of patients with PLAN and Kufor Rakep are limited, no statistical evaluation could be made. Discussion: These findings showed iron accumulation in GP has a key role in pathology of NBIA diseases. There is no significant correlation between the amount of iron and diseases course, age, gender and subgroups. Comparing iron measurements in atypical and typical PKAN patients and detection of more iron accumulation in the SN in atypical PKAN patients that may be associated with more frequent observation of parkinsonism than dystonia in clinical course. In healthy controls, more iron accumulation in putamen supports the pathology of NBIA diseases is not related to putamen. A correlation was found between iron accumulation and age in putamen in healthy controls, whereas there was correlation between age and amount of iron in putamen, substansia nigra and nucleus ruber of patients. This situation suggests that nucleus ruber and substantia nigra also has important role in the pathogenesis of the disease. Keywords: NBIA, QSM, basal ganglia, PKAN, MPAN, Kufor Rakeb Disease, PLAN, iron accumulation