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August 01, 2017; 89 (5) Article

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

María Sierra, Isabel Martínez-Rodríguez, Pascual Sánchez-Juan, Isabel González-Aramburu, Mikel Jiménez-Alonso, Antonio Sánchez-Rodríguez, José Berciano, Ignacio Banzo, Jon Infante
First published July 5, 2017, DOI: https://doi.org/10.1212/WNL.0000000000004185
María Sierra
From the Neurology Service (M.S., P.S.-J., I.G.-A., A.S.-R., J.B., J.I.), University Hospital Marqués de Valdecilla and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), IDIVAL, University of Cantabria (UC); and Nuclear Medicine Department (I.M.-R., M.J.-A., I.B.). Molecular Imaging Group (IDIVAL), University Hospital Marqués de Valdecilla, Santander, Spain.
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Isabel Martínez-Rodríguez
From the Neurology Service (M.S., P.S.-J., I.G.-A., A.S.-R., J.B., J.I.), University Hospital Marqués de Valdecilla and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), IDIVAL, University of Cantabria (UC); and Nuclear Medicine Department (I.M.-R., M.J.-A., I.B.). Molecular Imaging Group (IDIVAL), University Hospital Marqués de Valdecilla, Santander, Spain.
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Pascual Sánchez-Juan
From the Neurology Service (M.S., P.S.-J., I.G.-A., A.S.-R., J.B., J.I.), University Hospital Marqués de Valdecilla and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), IDIVAL, University of Cantabria (UC); and Nuclear Medicine Department (I.M.-R., M.J.-A., I.B.). Molecular Imaging Group (IDIVAL), University Hospital Marqués de Valdecilla, Santander, Spain.
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Isabel González-Aramburu
From the Neurology Service (M.S., P.S.-J., I.G.-A., A.S.-R., J.B., J.I.), University Hospital Marqués de Valdecilla and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), IDIVAL, University of Cantabria (UC); and Nuclear Medicine Department (I.M.-R., M.J.-A., I.B.). Molecular Imaging Group (IDIVAL), University Hospital Marqués de Valdecilla, Santander, Spain.
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Mikel Jiménez-Alonso
From the Neurology Service (M.S., P.S.-J., I.G.-A., A.S.-R., J.B., J.I.), University Hospital Marqués de Valdecilla and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), IDIVAL, University of Cantabria (UC); and Nuclear Medicine Department (I.M.-R., M.J.-A., I.B.). Molecular Imaging Group (IDIVAL), University Hospital Marqués de Valdecilla, Santander, Spain.
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Antonio Sánchez-Rodríguez
From the Neurology Service (M.S., P.S.-J., I.G.-A., A.S.-R., J.B., J.I.), University Hospital Marqués de Valdecilla and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), IDIVAL, University of Cantabria (UC); and Nuclear Medicine Department (I.M.-R., M.J.-A., I.B.). Molecular Imaging Group (IDIVAL), University Hospital Marqués de Valdecilla, Santander, Spain.
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José Berciano
From the Neurology Service (M.S., P.S.-J., I.G.-A., A.S.-R., J.B., J.I.), University Hospital Marqués de Valdecilla and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), IDIVAL, University of Cantabria (UC); and Nuclear Medicine Department (I.M.-R., M.J.-A., I.B.). Molecular Imaging Group (IDIVAL), University Hospital Marqués de Valdecilla, Santander, Spain.
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Ignacio Banzo
From the Neurology Service (M.S., P.S.-J., I.G.-A., A.S.-R., J.B., J.I.), University Hospital Marqués de Valdecilla and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), IDIVAL, University of Cantabria (UC); and Nuclear Medicine Department (I.M.-R., M.J.-A., I.B.). Molecular Imaging Group (IDIVAL), University Hospital Marqués de Valdecilla, Santander, Spain.
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Jon Infante
From the Neurology Service (M.S., P.S.-J., I.G.-A., A.S.-R., J.B., J.I.), University Hospital Marqués de Valdecilla and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), IDIVAL, University of Cantabria (UC); and Nuclear Medicine Department (I.M.-R., M.J.-A., I.B.). Molecular Imaging Group (IDIVAL), University Hospital Marqués de Valdecilla, Santander, Spain.
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Citation
Prospective clinical and DaT-SPECT imaging in premotor LRRK2 G2019S-associated Parkinson disease
María Sierra, Isabel Martínez-Rodríguez, Pascual Sánchez-Juan, Isabel González-Aramburu, Mikel Jiménez-Alonso, Antonio Sánchez-Rodríguez, José Berciano, Ignacio Banzo, Jon Infante
Neurology Aug 2017, 89 (5) 439-444; DOI: 10.1212/WNL.0000000000004185

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Abstract

Objective: 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.

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). Visual and semiquantitative analysis of images was performed. The specific striatal binding ratio was calculated (striatal region of interest [ROI] − occipital ROI/occipital ROI).

Results: 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.

Conclusions: 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.

GLOSSARY

DaT=
dopamine transporter;
PD=
Parkinson disease;
ROI=
region of interest;
SN=
substantia nigra;
UPDRS-III=
Unified Parkinson's Disease Rating Scale, part III;
UPSIT=
University of Pennsylvania Smell Identification Test

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received January 14, 2017.
  • Accepted in final form May 10, 2017.
  • © 2017 American Academy of Neurology
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