Nigro-striatal involvement in primary progressive freezing gait: insights into a heterogeneous pathogenesis

Primary progressive freezing gait (PPFG) is a clinical syndrome underlain by diverse neurodegenerative diseases and characterized by early occurrence of gait freezing. Either degeneration or integrity of the nigrostriatal terminals have been found by SPECT and PET studies. In this retrospective study, we evaluated (123)I-FP-CIT SPECT findings in a consecutive series of 13 PPFG patients with detailed clinical evaluation over time (mean follow-up duration: 3.1 ± 1.2 years). In all patients, (123)I-FP-CIT SPECT has been performed at the time of first clinical evaluation (1.7 ± 1.4 years after disease onset) and was compared with data from 23 age- and sex-matched healthy subjects. PPFG patients were categorized as having abnormal (n = 8) or normal (n = 5) SPECT. At disease onset, PPFG with abnormal SPECT had more frequent hypophonia, higher UPDRS-III scores and partial levodopa responsiveness. By contrast, PPFG with normal SPECT had more frequent bilateral plantar responses and no response to levodopa. At latest follow-up, initial diagnosis in the abnormal SPECT group was revised (n = 5) to progressive supranuclear palsy (n = 4) and pure akinesia with gait freezing (n = 1). Among the five patients with normal SPECT, follow-up evaluation disclosed corticobasal syndrome (n = 2) and primary lateral sclerosis (n = 1). Dopamine transporter imaging can capture the clinical heterogeneity of PPFG and might have a value to predict possible disease progression.