Relationship between 123I-FP-CIT-SPECT and gait impairments in drug-naïve individuals with Parkinson's disease

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by loss of nigrostriatal dopaminergic neurons [1]. In addition to cardinal motor symptoms, individuals with PD suffer of gait impairment [2]. Although functional imaging is useful for the diagnosis and pathophysiological evaluation of PD, little is known about the relationship between neuroimaging findings and PD clinical features. A study found a correlation between dopamine denervation and impaired gait automaticity [3]; others reported no association between dopaminergic denervation and some gait parameters, such as stride length and velocity [4,5], assuming that deficits in nondopaminergic neurotransmitter systems played the main role in gait impairments [3]. We aimed to examine the relationship between striatal dopaminergic depletion with disease severity in motor symptoms and gait variables in drug-naïve individuals with PD, in order to find where nigrostriatal pathway mainly acts. A total of 18 drug-naïve individuals with PD (mean age 70.4 ± 7.4 yrs) were enrolled. Motor symptoms were evaluated using the modified Hoehn and Yahr (H&Y) stage. Seven spatiotemporal variables of gait were acquired using a GAITRite® electronic walkway under comfortable walking, of which the coefficient of variation and the asymmetry were then calculated. The extent of striatal dopaminergic depletion was evaluated by dopamine transporter imaging with single-photon emission computed tomography using 123I-FP-CIT. Correlations between H&Y stage and gait variables with the specific binding ratios (SBRs) of the striatum (separated into putamen and caudate nucleus) were assessed with the Spearman's correlation coefficients (r). The mean SBRs of both the putamen and the caudate nucleus were significantly associated with the modified H&Y stage, with correlation coefficient of at least 0.60. A moderate correlation was found also between the asymmetry in the SBR of the putamen and the H&Y stage. Moreover, among the spatiotemporal gait variables, a moderate correlation was found between the mean double support duration and its asymmetry with the mean SBRs of both the putamen and the caudate nucleus (Table 1). On the contrary, stride length and velocity showed a weak correlation (below 0.30). Our findings suggest that both disease severity and gait impairments in early PD are associated with decreased dopamine binding in the striatum. Since the double support time showed a moderate correlation with dopaminergic depletion in particular in caudate nucleus, we propose this variable as a marker of the effect of nigrostriatal denervation on gait in individuals with early PD. On the other hand, the poor correlations found between the reduction of stride length and velocity with the nigrostriatal depletion confirmed the hypothesis of a major involvement of other systems (such as the cholinergic) in the control of these variables. Our findings supported the notion that a large part of gait impairments in PD resulted from multisystem degeneration [6,7].