Clinical features, disease progression, and nuclear imaging in ATXN2-related parkinsonism in a longitudinal cohort

Background Spinocerebellar ataxia 2 (SCA2) with a low range of CAG repeat expansion of ATXN2 gene can present with predominant or isolated parkinsonism that closely resembles Parkinson’s disease (PD). This study is aimed at comparing clinical features, disease progression, and nuclear imaging between ATXN2 -related parkinsonism ( ATXN2 -P) and PD. Methods Three hundred and seventy-seven clinically diagnosed PD with family history were screened by multiplex ligation-dependent probe amplification, whole-exome sequencing or target sequencing, and dynamic mutation testing of 10 SCA subtypes. The baseline and longitudinal clinical features as well as the dual-tracer positron emission tomography (PET) imaging were compared between ATXN2 -P and genetically undefined familial PD (GU-fPD). Results Fifteen ATXN2 -P patients from 7 families and 50 randomly selected GU-fPD patients were evaluated. Significantly less resting tremor and more symmetric signs were observed in ATXN2 -P than GU-fPD. No significant difference was found in motor progression and duration from onset to occurrence of fluctuation, dyskinesia, and recurrent falls between the two groups. Cognitive impairment and rapid-eye-movement sleep behavior disorder were more common in ATXN2 -P. During follow-up, olfaction was relatively spared, and no obvious progression of cognition dysfunction evaluated by Mini-Mental State Examination scores was found in ATXN2 -P. PET results of ATXN2 -P demonstrated a symmetric, diffuse, and homogenous dopamine transporter loss of bilateral striatum and a glucose metabolism pattern inconsistent with that in PD. Conclusions Symmetric motor signs and unique nuclear imaging might be the clues to distinguish ATXN2 -P from GU-fPD.