Contents lists available at ScienceDirect Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns Association of freezing of gait with nigral iron accumulation in patients with Parkinson's disease Rajini M. Naduthota a , Arush Arun Honnedevasthana e , Abhishek Lenka a,b , Jitender Saini c , Sairam Geethanath e , Rose Dawn Bharath c , Rita Christopher d , Ravi Yadav a , Arun Kumar Gupta c , Pramod Kumar Pal a,⁎ a Department of Neurology, National Institute of Mental Health & Neurosciences, Hosur Road, Bangalore 560029, Karnataka, India b Department of Clinical Neurosciences, National Institute of Mental Health & Neurosciences, Hosur Road, Bangalore 560029, Karnataka, India c Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health & Neurosciences, Hosur Road, Bangalore 560029, Karnataka, India d Department of Neurochemistry, National Institute of Mental Health & Neurosciences, Hosur Road, Bangalore 560029, Karnataka, India e Medical Imaging Research Center, Dayanand Sagar Institutions, Kumara Swamy Layout, Bangalore 560078, India ARTICLE INFO Keywords: Parkinson's disease Freezing R2* relaxometry Gait ABSTRACT Background and purpose: The objective of this work was to investigate whether patients with and without freezing of gait (FOG) in Parkinson's disease (PD) have differences in iron accumulation in substantia nigra using R2* relaxometry. Materials and methods: This study included seventeen PD patients with FOG [FOG (+)], equal number of age and gender matched patients without FOG [FOG (-)] and 34 healthy controls (HC). T2* images were obtained from a 3-Tesla MRI system using multi-echo sequence. R2* values were extracted from Substantia Nigra (SN) and red nucleus and were compared among the three groups and correlated with clinical findings. Results: R2* values were increased in PD group as a whole compared to HC in rostral and caudal segments of Substantia Nigra pars compacta (SNc) and in Substantia Nigra pars reticulata (SNr) but not in red nucleus. Within PD subgroups, FOG (+) group had increased iron accumulation in SNc compared to FOG (-) and HC. FOG score positively correlated with R2* values in the caudal region of SNc in FOG (+) group. Conclusions: Our study reveals higher nigral iron content in FOG (+) compared to FOG (-) and HCs. In ad- dition, we observed positive correlation of FOG score with iron accumulation in SNc. Results of this study emphasize possible role of higher nigral iron content in the pathogenesis of FOG in PD. 1. Introduction Parkinson's disease (PD) is a progressive, neurodegenerative dis- order and its cardinal motor symptoms include tremor at rest, rigidity, bradykinesia and postural instability [1]. In addition, several non- motor symptoms such as cognitive impairment, depression, autonomic dysfunction, and sleep disturbances may emerge during the course of the illness [2]. Loss of dopaminergic neurons in substantia nigra (SN) along with accumulation of Lewy bodies in several parts of the brain is the pathological hallmark of PD [3]. Autopsy studies as well as neu- roimaging studies have reported greater accumulation of iron in SN of patients with PD compared to healthy controls (HC) [4,5]. It has been speculated that excessive iron accumulation is partially responsible for generation of reactive oxygen species resulting in accelerated loss of dopaminergic neurons in SN in PD [6]. Disturbances of gait and balance are common in patients with PD. Freezing of gait (FOG) is one of the disabling disturbances related to gait characterized by episodic absence or marked reduction of forward progression of feet despite the intention to walk which lasts for a brief duration [7]. Although longer duration, higher stage and increased severity of PD have been reported to have association with FOG, exact neural correlates of FOG still remain elusive [8]. Several studies using advanced structural and functional neuroi- maging techniques have attempted to explore the neural correlates of FOG in patients with PD. However, the results have not been uniform enough to draw any conclusive evidence. Studies based on structural neuroimaging have reported abnormalities in white matter tracts in pedunculopontine nucleus, orbitofrontal cortex, primary as well as supplementary motor cortex and widespread grey matter atrophy [9,10]. Functional neuroimaging studies have shown reduced inter- http://dx.doi.org/10.1016/j.jns.2017.09.033 Received 25 May 2017; Received in revised form 8 August 2017; Accepted 22 September 2017 ⁎ Corresponding author. E-mail address: palpramod@nimhans.ac.in (P.K. Pal). Journal of the Neurological Sciences 382 (2017) 61–65 Available online 23 September 2017 0022-510X/ © 2017 Elsevier B.V. All rights reserved. MARK