Prospective clinical and DaT-SPECT imaging in premotor LRRK2 G2019S-associated Parkinson disease.

María Sierra,Pascual Sánchez-Juan,Mikel Jiménez-Alonso,Ignacio Banzo,Antonio Sánchez-Rodríguez,Jon Infante,Isabel González-Aramburu,Isabel Martínez-Rodríguez,José Berciano

doi:10.1212/wnl.0000000000004185

Abstract

To assess the value of baseline clinical and imaging biomarkers in a cohort of asymptomatic LRRK2 G2019S carriers for predicting conversion to Parkinson disease (PD) at 4 years. Thirty-two asymptomatic carriers of LRRK2 G2019S mutation underwent baseline and 4-year evaluation including clinical examination (Unified Parkinson's Disease Rating Scale, part III, olfaction University of Pennsylvania Smell Identification Test [UPSIT]) and dopamine transporter (DaT) SPECT (123I-ioflupane). Visual and semiquantitative analysis of images was performed. The specific striatal binding ratio was calculated (striatal region of interest [ROI] - occipital ROI/occipital ROI). Three carriers, asymptomatic at baseline, had converted to PD at 4-year evaluation. Twenty-three participants were fully evaluated. PD converters had lower striatal DaT binding at baseline than nonconverters (p = 0.002). A baseline scan with a ratio of bilateral striatal uptake below 1 predicted conversion to PD within the 4-year period with high sensitivity and specificity (area under the curve 1; p = 0.006). The slope of DaT binding decline between the 2 scans was similar in PD converters and nonconverters. Age-adjusted UPSIT score at baseline and at 4 years was similar in both groups. Semiquantitative DaT-SPECT could be used to predict early conversion to PD in asymptomatic carriers of the LRRK2 G2019S mutation. Rate of conversion to PD at 4 years in this cohort aged ∼64 years was 12%. The slope of DaT binding decline on DaT-SPECT imaging seems to be similar across different stages of the premotor period.

Highlights

Semiquantitative dopamine transporter (DaT)-SPECT could be used to predict early conversion to Parkinson disease (PD) in asymptomatic carriers of the LRRK2 G2019S mutation
All of them were relatives of LRRK2 G2019S PD proband cases identified from a study of 367 consecutive patients with PD attended at a single center.[2]
In cases in which the examination led to a diagnosis of PD, we acceded to patient clinical records to check if the patient had already been diagnosed with PD within the 4-year period

Summary

Methods

Thirty-two asymptomatic carriers of LRRK2 G2019S mutation underwent baseline and 4-year evaluation including clinical examination (Unified Parkinson’s Disease Rating Scale, part III, olfaction University of Pennsylvania Smell Identification Test [UPSIT]) and dopamine transporter (DaT) SPECT (123I-ioflupane). We used the Unified Parkinson’s Disease Rating Scale, part III (UPDRS-III), and a diagnosis of PD was made according to the Queen Square Brain Bank Criteria.[4] All participants were assessed at a single center and by the same research team involved in the baseline evaluation, in which examiners were blind to the genetic status of LRRK2 relatives.[3] Clinical examination was done before the rest of the tests were available so examiners were blind to these results. In cases in which the examination led to a diagnosis of PD, we acceded to patient clinical records to check if the patient had already been diagnosed with PD within the 4-year period

Results

Discussion

Conclusion