N. Piramide1,2, F. Agosta1,2, E. Sarasso1,2, T. Stojkovic3, I. Stankovic3, S. Basaia1, A. Tomic3, V. Markovic3, E. Stefanova3, V.S. Kostic3, M. Filippi1,4,5,2
1IRCCS San Raffaele Scientific Institute, Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Milan, Italy, 2Vita-Salute San Raffaele University, Milan, Italy, 3University of Belgrade, Clinic of Neurology, Faculty of Medicine, Belgrade, Serbia, 4IRCCS San Raffaele Scientific Institute, Neurology Unit, Milan, Italy, 5IRCCS San Raffaele Scientific Institute, Neurophysiology Unit, Milan, Italy
Background: In Parkinson’s disease (PD), freezing of gait (FoG) is a disabling phenomenon. The pathophysiology underlying FoG is still unclear and, to date, no longitudinal studies have explored brain structural alterations in PD patients with FoG (PD-FoG) over time.
Purpose: The main objective of this study is to investigate the cortical and subcortical grey matter (GM) changes in PD-FoG over one and two years of follow-up. We also investigated GM features of PD patients developing FoG (PD-FoG-converters) within two years.
Methods: Thirty PD-FoG and 11 PD-FoG-converters patients were recruited. Patients underwent 3D T1-weighted magnetic resonance imaging. Whole brain cortical thickness and volumes of basal ganglia, thalamus, nucleus accumbens, amygdala and hippocampus were assessed. Paired t test corrected for multiple comparisons using the Bonferroni procedure at p<0.05 were used to assess GM changes over one and two years of follow-up in PD-FoG and PD-FoG-converters patients.
Results: Both PD-FoG and PD-FoG-converters patients showed no cortical thickness changes over time. The analysis of GM volumes showed that PD-FoG patients presented decreased volume of the right putamen between baseline and one year and reduced volume of left pallidum, right thalamus and hippocampus between one and two years of follow-up. Moreover, PD-FoG-converters showed GM atrophy accumulation in the right putamen and hippocampus between baseline and two years and of the right putamen between one and two years of follow-up.
Conclusion(s): These findings suggested that PD-FoG-converters are characterized by an accumulation of GM atrophy in the putamen and hippocampus, which probably predispose to FoG development. PD-FoG patients continued to accumulate GM atrophy in these areas together with pallidum and thalamus that are progressively involved as the FoG symptoms worsened. PD-FoG and PD-FoG-converters are characterized by a progressive accumulation of GM atrophy in areas involved both in motor and cognitive functions such as basal ganglia and hippocampus. These findings support the hypothesis concerning the problematic interplay between motor and cognitive circuits in the underlying mechanisms of FoG in PD.
Implications: Having a clearer view about the pathophysiological mechanisms underlying FoG could help clinicians to better manage this phenomenon ameliorating quality of life and social participation of PD patients.
Funding, acknowledgements: This study was supported by the Ministry of Education, Science, and Technological Development of the Republic of Serbia (project #175090).
Keywords: Parkinson’s disease, longitudinal study, brain structural alterations
Topic: Neurology: Parkinson's disease
Did this work require ethics approval? Yes
Institution: Clinic of Neurology, Faculty of Medicine, University of Belgrade, Serbia
Committee: Human Research Ethics Committee of University of Belgrade, Serbia
Ethics number: Belgrade project #175090
All authors, affiliations and abstracts have been published as submitted.
