GBA1 variants and dopaminergic imaging in essential tremor with atypical features: A comparative study with Parkinson's disease.

INTRODUCTION

Essential tremor (ET) is a prevalent movement disorder in which a subset of patients presents with additional neurological signs such as rest tremor, impaired gait, or subtle parkinsonian features. This phenotype has been referred to as "ET plus" in recent classification proposals, although its biological validity remains uncertain. To investigate possible overlap with Parkinson's disease (PD), we assessed clinical, imaging, and genetic features of this subgroup.

METHODS

We studied 101 patients with PD and 36 patients with ET plus at the stage of initial diagnostic work-up, when presynaptic dopamine transporter (DAT) imaging was clinically indicated. All patients underwent [123I]FP-CIT SPECT, structured neurological assessment, and genotyping for four common PD-associated GBA1 variants (p.Asn409Ser, p.Leu483Pro, p.Glu365Lys, and p.Thr408Met).

RESULTS

The prevalence of GBA1 variants did not differ between PD (16 %) and ET plus (19 %) (p = 0.61). All patients in the ET group had normal striatal DAT binding, whereas PD patients showed mean reductions of 57-67 % in the posterior putamen. No significant differences in DAT binding or clinical characteristics were observed between GBA1-positive and GBA1-negative patients within either group.

CONCLUSION

In this exploratory study, the observed frequencies of GBA1 variants in PD and ET plus patients did not differ. Moreover, we did not detect any measurable dopaminergic dysfunction or distinct clinical profiles related to the GBA1 variants at the diagnostic stage. Longitudinal studies are warranted to explore the phenotype of GBA1-positive ET plus in detail.