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Prospective clinical and DaT-SPECT imaging in premotor LRRK2 G2019S-associated Parkinson disease.
Neurology. 2017 Aug 01; 89(5):439-444.Neur

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.

Authors+Show Affiliations

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.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.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.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.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.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.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.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.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. jinfante@humv.es.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28679601

Citation

Sierra, María, et al. "Prospective Clinical and DaT-SPECT Imaging in Premotor LRRK2 G2019S-associated Parkinson Disease." Neurology, vol. 89, no. 5, 2017, pp. 439-444.
Sierra M, Martínez-Rodríguez I, Sánchez-Juan P, et al. Prospective clinical and DaT-SPECT imaging in premotor LRRK2 G2019S-associated Parkinson disease. Neurology. 2017;89(5):439-444.
Sierra, M., Martínez-Rodríguez, I., Sánchez-Juan, P., González-Aramburu, I., Jiménez-Alonso, M., Sánchez-Rodríguez, A., Berciano, J., Banzo, I., & Infante, J. (2017). Prospective clinical and DaT-SPECT imaging in premotor LRRK2 G2019S-associated Parkinson disease. Neurology, 89(5), 439-444. https://doi.org/10.1212/WNL.0000000000004185
Sierra M, et al. Prospective Clinical and DaT-SPECT Imaging in Premotor LRRK2 G2019S-associated Parkinson Disease. Neurology. 2017 Aug 1;89(5):439-444. PubMed PMID: 28679601.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prospective clinical and DaT-SPECT imaging in premotor LRRK2 G2019S-associated Parkinson disease. AU - Sierra,María, AU - Martínez-Rodríguez,Isabel, AU - Sánchez-Juan,Pascual, AU - González-Aramburu,Isabel, AU - Jiménez-Alonso,Mikel, AU - Sánchez-Rodríguez,Antonio, AU - Berciano,José, AU - Banzo,Ignacio, AU - Infante,Jon, Y1 - 2017/07/05/ PY - 2017/01/14/received PY - 2017/05/10/accepted PY - 2017/7/7/pubmed PY - 2017/8/5/medline PY - 2017/7/7/entrez SP - 439 EP - 444 JF - Neurology JO - Neurology VL - 89 IS - 5 N2 - 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. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/28679601/Prospective_clinical_and_DaT_SPECT_imaging_in_premotor_LRRK2_G2019S_associated_Parkinson_disease_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=28679601 DB - PRIME DP - Unbound Medicine ER -