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Substantia Nigra Neuromelanin as an Imaging Biomarker of Disease Progression in Parkinson's Disease.
J Parkinsons Dis. 2017; 7(3):491-501.JP

Abstract

BACKGROUND

A specific T1-weighted magnetic resonance imaging (MRI) sequence has been shown to detect substantia nigra (SN) neuromelanin (NM) signal changes that accurately discriminate Parkinson's disease (PD) patients from controls, even in early disease stages. However, it is unclear what happens to these SN changes in later disease stages and if they can be a marker of disease progression.

OBJECTIVE

to investigate the pattern of SN-NM area loss and contrast ratio (CR) intensity changes in late-stage PD (LSPD) compared to earlier disease stages.

METHODS

A comparative cross-sectional study was performed, analyzing SN-NM MRI signal in LSPD (Schwab and England Activities of Daily Living Scale score <50 or Hoehn Yahr Stage [HY] >3), comparing this group with de novo, 2-5 year PD and controls. SN-NM signal area and CR values for the internal and lateral SN regions were obtained with semi-automated methods.

RESULTS

13 LSPD, 12 de novo patients with PD, 10 PD patients with a 2-5 year disease duration, and 10 controls were included. NM signal area was significantly decreased in LSPD compared to de novo PD (P-value = 0.005; sensitivity: 75%; specificity 92% and AUC: 0.86). In the lateral SN region, a decrease in the CR was detected in all PD groups compared to controls; despite not reaching statistical significance, a slight increment was observed comparing LSPD to 2-5 year PD. NM signal area significantly correlated with HY (R = -0.37; P < 0.05) and Movement disorder Society Unified Parkinson's Disease Rating Scale part II (MDS-UPDRS) (R = -0.4; P < 0.05) while a weak correlation was found with MDS-UPDRS part III (R = -0.26; P: 0.1).

CONCLUSION

SN area evaluated by NM-sensitive MRI may be a promising biomarker of nigral degeneration and disease progression in PD patients.

Authors+Show Affiliations

Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal. Department of Neurological Imaging, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.Instituto de Biofísica e Engenharia Biomédica, Faculdade de Ciências, University of Lisbon, Lisbon, Portugal.Instituto de Biofísica e Engenharia Biomédica, Faculdade de Ciências, University of Lisbon, Lisbon, Portugal. Department of Bioengineering and Institute for Systems and Robotics (LARSyS), Instituto Superior Técnico, University of Lisbon, Lisbon, Portugal.Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal. Department of Neurosciences, Hospital Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal. Center for Interdisciplinary Research Egas Moniz(CiiEM), Instituto Superior de Ciências da Saúde EgasMoniz, Monte de Caparica, Portugal. CNS - Campus Neurológico Sénior, Torres Vedras, Portugal.Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal. Department of Neurosciences, Hospital Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal. Department of Neurosciences, Hospital Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.Fondazione Ospedale San Camillo"-I.R.C.C.S., Parkinson and Movement Disorders Unit, Venice, Italy.Clinical Pharmacology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal. CNS - Campus Neurológico Sénior, Torres Vedras, Portugal. Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28671143

Citation

Fabbri, Margherita, et al. "Substantia Nigra Neuromelanin as an Imaging Biomarker of Disease Progression in Parkinson's Disease." Journal of Parkinson's Disease, vol. 7, no. 3, 2017, pp. 491-501.
Fabbri M, Reimão S, Carvalho M, et al. Substantia Nigra Neuromelanin as an Imaging Biomarker of Disease Progression in Parkinson's Disease. J Parkinsons Dis. 2017;7(3):491-501.
Fabbri, M., Reimão, S., Carvalho, M., Nunes, R. G., Abreu, D., Guedes, L. C., Bouça, R., Lobo, P. P., Godinho, C., Coelho, M., Gonçalves, N. C., Rosa, M. M., Antonini, A., & Ferreira, J. J. (2017). Substantia Nigra Neuromelanin as an Imaging Biomarker of Disease Progression in Parkinson's Disease. Journal of Parkinson's Disease, 7(3), 491-501. https://doi.org/10.3233/JPD-171135
Fabbri M, et al. Substantia Nigra Neuromelanin as an Imaging Biomarker of Disease Progression in Parkinson's Disease. J Parkinsons Dis. 2017;7(3):491-501. PubMed PMID: 28671143.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Substantia Nigra Neuromelanin as an Imaging Biomarker of Disease Progression in Parkinson's Disease. AU - Fabbri,Margherita, AU - Reimão,Sofia, AU - Carvalho,Miguel, AU - Nunes,Rita G, AU - Abreu,Daisy, AU - Guedes,Leonor Correia, AU - Bouça,Raquel, AU - Lobo,Patricia P, AU - Godinho,Catarina, AU - Coelho,Miguel, AU - Gonçalves,Nilza C, AU - Rosa,Mario Miguel, AU - Antonini,Angelo, AU - Ferreira,Joaquim J, PY - 2017/7/4/pubmed PY - 2018/5/1/medline PY - 2017/7/4/entrez KW - Neuromelanin KW - Parkinson’s disease KW - biomarker KW - disease progression KW - late-stage SP - 491 EP - 501 JF - Journal of Parkinson's disease JO - J Parkinsons Dis VL - 7 IS - 3 N2 - BACKGROUND: A specific T1-weighted magnetic resonance imaging (MRI) sequence has been shown to detect substantia nigra (SN) neuromelanin (NM) signal changes that accurately discriminate Parkinson's disease (PD) patients from controls, even in early disease stages. However, it is unclear what happens to these SN changes in later disease stages and if they can be a marker of disease progression. OBJECTIVE: to investigate the pattern of SN-NM area loss and contrast ratio (CR) intensity changes in late-stage PD (LSPD) compared to earlier disease stages. METHODS: A comparative cross-sectional study was performed, analyzing SN-NM MRI signal in LSPD (Schwab and England Activities of Daily Living Scale score <50 or Hoehn Yahr Stage [HY] >3), comparing this group with de novo, 2-5 year PD and controls. SN-NM signal area and CR values for the internal and lateral SN regions were obtained with semi-automated methods. RESULTS: 13 LSPD, 12 de novo patients with PD, 10 PD patients with a 2-5 year disease duration, and 10 controls were included. NM signal area was significantly decreased in LSPD compared to de novo PD (P-value = 0.005; sensitivity: 75%; specificity 92% and AUC: 0.86). In the lateral SN region, a decrease in the CR was detected in all PD groups compared to controls; despite not reaching statistical significance, a slight increment was observed comparing LSPD to 2-5 year PD. NM signal area significantly correlated with HY (R = -0.37; P < 0.05) and Movement disorder Society Unified Parkinson's Disease Rating Scale part II (MDS-UPDRS) (R = -0.4; P < 0.05) while a weak correlation was found with MDS-UPDRS part III (R = -0.26; P: 0.1). CONCLUSION: SN area evaluated by NM-sensitive MRI may be a promising biomarker of nigral degeneration and disease progression in PD patients. SN - 1877-718X UR - https://www.unboundmedicine.com/medline/citation/28671143/Substantia_Nigra_Neuromelanin_as_an_Imaging_Biomarker_of_Disease_Progression_in_Parkinson's_Disease_ L2 - https://content.iospress.com/openurl?genre=article&amp;id=doi:10.3233/JPD-171135 DB - PRIME DP - Unbound Medicine ER -