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Original Investigation
October 10, 2016

Subregional Pattern of Striatal Dopamine Transporter Loss on 18F FP-CIT Positron Emission Tomography in Patients With Pure Akinesia With Gait Freezing

Author Affiliations
  • 1Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
  • 2Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
  • 3Department of Neurology, Inje University Ilsan-Paik Hospital, Goyang, Republic of Korea
JAMA Neurol. Published online October 10, 2016. doi:10.1001/jamaneurol.2016.3243
Key Points

Question  Is the subregional pattern of striatal dopamine transporter loss in patients with pure akinesia with gait freezing similar to that in patients with progressive supranuclear palsy?

Findings  In this case-control study using F-18-fluorinated-N-3-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl)-nortropane (18F FP-CIT) positron emission tomography, the preferential subregional pattern of striatal dopamine transporter loss in patients with pure akinesia with gait freezing was similar to that in patients with progressive supranuclear palsy, which results from early dopamine transporter loss in the caudate nuclei, but not to that in patients with Parkinson disease.

Meaning  These results suggest a similar distribution of regional neuronal loss in the substantia nigra pars compacta between pure akinesia with gait freezing and progressive supranuclear palsy.

Abstract

Importance  Pure akinesia with gait freezing (PAGF) is a clinical syndrome characterized by freezing of gait, handwriting, and speech without abnormal eye movement or cognitive impairment. Several studies have suggested that PAGF may be a variant of progressive supranuclear palsy (PSP). However, the characteristics of striatal dopamine transporter loss in PAGF are unknown.

Objective  To investigate the subregional pattern of striatal dopamine transporter loss in patients with PAGF in comparison with patients with PSP and those with Parkinson disease (PD).

Design, Setting, and Participants  This retrospective case-control study included 15 patients with PAGF, 27 with PD, 20 with PSP, and 11 healthy controls who underwent F-18-fluorinated-N-3-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl)-nortropane (18F FP-CIT) positron emission tomography between September 1, 2008, and July 31, 2014. The positron emission tomographic images were analyzed with 12 striatal subregional and 1 occipital volume-of-interest templates. The specific to nonspecific binding ratio (SNBR) and intersubregional ratio (ISR) in patients with PAGF were compared with those in patients with PD and those with PSP.

Main Outcomes and Measures  Comparisons of SNBRs of striatal subregions and ISR among patients with PAGF, PD, and PSP and healthy controls.

Results  The mean (SD) SNBRs (1.4 [0.7]) of the whole striatum in the 15 patients with PAGF (mean [SD] age, 71.4 [6.6] years; 7 men and 8 women) were similar to those in the 20 patients (mean [SD] age, 70.6 [4.5] years; 11 men and 9 women) with PSP (1.5 [0.5]) but significantly lower than those in the 27 patients (mean [SD] age, 67.7 [5.3] years; 10 men and 17 women) with PD (3.0 [1.3]). The mean (SD) SNBRs of the caudate nuclei in patients with PAGF (1.3 [0.9]) were significantly lower than those in patients with PD (3.5 [1.5]; P < .001) but slightly higher than those in patients with PSP (1.2 [0.5]). The mean [SD] anterior caudate to ventral striatum ISRs in patients with PAGF (0.5 [0.3]) were similar to those in patients with PSP (0.4 [0.2]) but not in patients with PD (1.0 [0.2]). The mean (SD) posterior to anterior putamen ISRs in patients with PAGF (0.4 [0.2]) were similar to those in patients with PD (0.5 [0.2]) and those with PSP (0.4 [0.2]).

Conclusions and Relevance  On 18F FP-CIT positron emission tomography, patients with PAGF show a pattern of preferential dopaminergic loss similar to that seen in patients with PSP. These results suggest a similar distribution of regional neuronal loss in the substantia nigra pars compacta between PAGF and PSP. This finding may be one of the pathophysiological results suggesting that PAGF is a phenotypic variant of PSP.

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