Vol.:(0123456789) 1 3 J Neurol DOI 10.1007/s00415-017-8654-1 ORIGINAL COMMUNICATION Freezing of gait in Parkinson’s disease: gray and white matter abnormalities Sara Pietracupa 1  · Antonio Suppa 1,2  · Neeraj Upadhyay 2  · Costanza Giannì 2  · Giovanni Grillea 1  · Giorgio Leodori 2  · Nicola Modugno 1  · Francesca Di Biasio 1  · Alessandro Zampogna 2  · Claudio Colonnese 1,2  · Alfredo Berardelli 1,2  · Patrizia Pantano 1,2   Received: 14 July 2017 / Revised: 16 October 2017 / Accepted: 21 October 2017 © Springer-Verlag GmbH Germany 2017 Keywords Parkinson’s disease · Freezing of gait · Magnetic resonance imaging · Cortical thickness · Difusion tensor imaging Introduction Freezing of gait (FOG) is a disabling disorder that often afects Parkinson’s disease (PD) patients in the advanced stages [1] and is characterized by difculty in voluntary gait [2]. Step initiation, change in direction and walking through a narrow space classically elicit FOG [3]. The pathophysiol- ogy of FOG in PD is still unclear and the clinical manage- ment of this disorder remains challenging [4–6]. Magnetic resonance imaging (MRI) studies on PD patients with FOG (PD-FOG) have revealed a number of structural brain abnormalities in both gray (GM) and white matter (WM). Voxel-based morphometry (VBM) studies have detected GM loss in several cortical regions, mainly located in the parietal, temporal and occipital lobes as well as in the dorsolateral prefrontal cortex (DLPFC), thereby suggesting that atrophy in these regions may play a role in the pathophysiology of FOG [7–11]. The thalamus, caudate and brainstem regions may also display volumetric GM changes in PD-FOG patients [12–14]. Difusion tensor imag- ing (DTI) studies have revealed white matter (WM) damage, as demonstrated by abnormal fractional anisotropy (FA) and radial (RD), mean (MD) and axial (AxD) difusivity in long- range associative bundles, including the superior longitudi- nal fasciculus (SLF) and the corpus callosum [15–18]. The surface-based method (SBM) is a technique that may give further insights into GM abnormalities in PD- FOG patients as it may provide more detailed informa- tion on microstructural changes in GM. Unlike VBM, the SBM yields more specifc information on GM changes by Abstract Freezing of gait (FOG) is a disabling disor- der that often afects Parkinson’s disease (PD) patients in advanced stages of the disease. To study structural gray mat- ter (GM) and white matter (WM) changes in PD patients with and without FOG, twenty-one PD patients with FOG (PD-FOG), 16 PD patients without FOG (PD-nFOG) and 19 healthy subjects (HS) underwent a standardized MRI protocol. For the gray matter evaluation, cortical volume (CV), cortical thickness (CTh), and surface area (SA) were analyzed using the FreeSurfer pipeline. For the white mat- ter evaluation, DTI images were analyzed using tracts con- strained by underlying anatomy (TRACULA) toolbox in FreeSurfer. PD-FOG patients exhibited lower CTh than HS in the mesial surface of both cerebral hemispheres, includ- ing the superior frontal gyrus, paracentral lobule, posterior cingulate cortex, precuneus and pericalcarine cortex, and in the right dorsolateral prefrontal cortex. Moreover, sig- nifcant WM changes were observed in PD-FOG patients in comparison with HS in the superior longitudinal fasciculus, uncinate fasciculus, cingulum cingulate gyrus and inferior longitudinal fasciculus (prevalently in the right hemisphere) and in the frontal radiations of the corpus callosum. DTI abnormalities in specifc WM bundles correlated signif- cantly with cognitive measures. The damage of multiple cortical areas involved in high-level gait control together with WM disruption between motor, cognitive and limbic structures may represent the anatomical correlate of FOG. * Patrizia Pantano patrizia.pantano@uniroma1.it 1 IRCCS Neuromed Institute, Pozzilli, IS, Italy 2 Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy