Premotor Parkinson's disease: Concepts and definitions
Parkinson's disease (PD) has a prodromal phase during which nonmotor clinical features as well as physiological abnormalities may be present. These premotor markers could be used to screen for PD before motor abnormalities are present. The technology to identify PD before it reaches symptomatic...
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| Published in | Movement disorders Vol. 27; no. 5; pp. 608 - 616 |
|---|---|
| Main Authors | , |
| Format | Journal Article |
| Language | English |
| Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
15.04.2012
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| Online Access | Get full text |
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| Abstract | Parkinson's disease (PD) has a prodromal phase during which nonmotor clinical features as well as physiological abnormalities may be present. These premotor markers could be used to screen for PD before motor abnormalities are present. The technology to identify PD before it reaches symptomatic Braak Stage 3 (substantia nigra compacta [SNc] involvement) already exists. The current challenge is to define the appropriate scope of use of predictive testing for PD. Imaging technologies such as dopamine transporter imaging currently offer the highest degree of accuracy for identifying premotor PD, but they are expensive as screening tools, and abnormalities on these studies would only be evident at Braak Stage 3 or higher. Efficiency is greatly enhanced by combining imaging with a prescreening test such as olfactory testing. This 2‐step process has the potential to greatly reduce costs while retaining diagnostic accuracy. Alternatively, or in concert with this approach, evaluating high‐risk populations (eg, patients with rapid eye movement behavior disorder or LRRK2 mutations) would enrich the sample for cases with underlying PD. Ultimately, the role of preclinical detection of PD will be determined by the ability of emerging therapies to influence clinical outcomes. As such, implementation of large‐scale screening strategies awaits the arrival of clearly safe and effective therapies that address the underlying pathogenesis of PD. Future research will establish more definitive biomarkers capable of revealing the presence of disease in advance of SNc involvement with the promise of the potential for introducing disease‐modifying therapy even before the development of evidence of dopamine deficiency. © 2012 Movement Disorder Society |
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| AbstractList | Parkinson's disease (PD) has a prodromal phase during which nonmotor clinical features as well as physiological abnormalities may be present. These premotor markers could be used to screen for PD before motor abnormalities are present. The technology to identify PD before it reaches symptomatic Braak Stage 3 (substantia nigra compacta [SNc] involvement) already exists. The current challenge is to define the appropriate scope of use of predictive testing for PD. Imaging technologies such as dopamine transporter imaging currently offer the highest degree of accuracy for identifying premotor PD, but they are expensive as screening tools, and abnormalities on these studies would only be evident at Braak Stage 3 or higher. Efficiency is greatly enhanced by combining imaging with a prescreening test such as olfactory testing. This 2‐step process has the potential to greatly reduce costs while retaining diagnostic accuracy. Alternatively, or in concert with this approach, evaluating high‐risk populations (eg, patients with rapid eye movement behavior disorder or
LRRK2
mutations) would enrich the sample for cases with underlying PD. Ultimately, the role of preclinical detection of PD will be determined by the ability of emerging therapies to influence clinical outcomes. As such, implementation of large‐scale screening strategies awaits the arrival of clearly safe and effective therapies that address the underlying pathogenesis of PD. Future research will establish more definitive biomarkers capable of revealing the presence of disease in advance of SNc involvement with the promise of the potential for introducing disease‐modifying therapy even before the development of evidence of dopamine deficiency. © 2012 Movement Disorder Society Parkinson's disease (PD) has a prodromal phase during which nonmotor clinical features as well as physiological abnormalities may be present. These premotor markers could be used to screen for PD before motor abnormalities are present. The technology to identify PD before it reaches symptomatic Braak Stage 3 (substantia nigra compacta [SNc] involvement) already exists. The current challenge is to define the appropriate scope of use of predictive testing for PD. Imaging technologies such as dopamine transporter imaging currently offer the highest degree of accuracy for identifying premotor PD, but they are expensive as screening tools, and abnormalities on these studies would only be evident at Braak Stage 3 or higher. Efficiency is greatly enhanced by combining imaging with a prescreening test such as olfactory testing. This 2-step process has the potential to greatly reduce costs while retaining diagnostic accuracy. Alternatively, or in concert with this approach, evaluating high-risk populations (eg, patients with rapid eye movement behavior disorder or LRRK2 mutations) would enrich the sample for cases with underlying PD. Ultimately, the role of preclinical detection of PD will be determined by the ability of emerging therapies to influence clinical outcomes. As such, implementation of large-scale screening strategies awaits the arrival of clearly safe and effective therapies that address the underlying pathogenesis of PD. Future research will establish more definitive biomarkers capable of revealing the presence of disease in advance of SNc involvement with the promise of the potential for introducing disease-modifying therapy even before the development of evidence of dopamine deficiency.Parkinson's disease (PD) has a prodromal phase during which nonmotor clinical features as well as physiological abnormalities may be present. These premotor markers could be used to screen for PD before motor abnormalities are present. The technology to identify PD before it reaches symptomatic Braak Stage 3 (substantia nigra compacta [SNc] involvement) already exists. The current challenge is to define the appropriate scope of use of predictive testing for PD. Imaging technologies such as dopamine transporter imaging currently offer the highest degree of accuracy for identifying premotor PD, but they are expensive as screening tools, and abnormalities on these studies would only be evident at Braak Stage 3 or higher. Efficiency is greatly enhanced by combining imaging with a prescreening test such as olfactory testing. This 2-step process has the potential to greatly reduce costs while retaining diagnostic accuracy. Alternatively, or in concert with this approach, evaluating high-risk populations (eg, patients with rapid eye movement behavior disorder or LRRK2 mutations) would enrich the sample for cases with underlying PD. Ultimately, the role of preclinical detection of PD will be determined by the ability of emerging therapies to influence clinical outcomes. As such, implementation of large-scale screening strategies awaits the arrival of clearly safe and effective therapies that address the underlying pathogenesis of PD. Future research will establish more definitive biomarkers capable of revealing the presence of disease in advance of SNc involvement with the promise of the potential for introducing disease-modifying therapy even before the development of evidence of dopamine deficiency. Parkinson's disease (PD) has a prodromal phase during which nonmotor clinical features as well as physiological abnormalities may be present. These premotor markers could be used to screen for PD before motor abnormalities are present. The technology to identify PD before it reaches symptomatic Braak Stage 3 (substantia nigra compacta [SNc] involvement) already exists. The current challenge is to define the appropriate scope of use of predictive testing for PD. Imaging technologies such as dopamine transporter imaging currently offer the highest degree of accuracy for identifying premotor PD, but they are expensive as screening tools, and abnormalities on these studies would only be evident at Braak Stage 3 or higher. Efficiency is greatly enhanced by combining imaging with a prescreening test such as olfactory testing. This 2-step process has the potential to greatly reduce costs while retaining diagnostic accuracy. Alternatively, or in concert with this approach, evaluating high-risk populations (eg, patients with rapid eye movement behavior disorder or LRRK2 mutations) would enrich the sample for cases with underlying PD. Ultimately, the role of preclinical detection of PD will be determined by the ability of emerging therapies to influence clinical outcomes. As such, implementation of large-scale screening strategies awaits the arrival of clearly safe and effective therapies that address the underlying pathogenesis of PD. Future research will establish more definitive biomarkers capable of revealing the presence of disease in advance of SNc involvement with the promise of the potential for introducing disease-modifying therapy even before the development of evidence of dopamine deficiency. Parkinson's disease (PD) has a prodromal phase during which nonmotor clinical features as well as physiological abnormalities may be present. These premotor markers could be used to screen for PD before motor abnormalities are present. The technology to identify PD before it reaches symptomatic Braak Stage 3 (substantia nigra compacta [SNc] involvement) already exists. The current challenge is to define the appropriate scope of use of predictive testing for PD. Imaging technologies such as dopamine transporter imaging currently offer the highest degree of accuracy for identifying premotor PD, but they are expensive as screening tools, and abnormalities on these studies would only be evident at Braak Stage 3 or higher. Efficiency is greatly enhanced by combining imaging with a prescreening test such as olfactory testing. This 2‐step process has the potential to greatly reduce costs while retaining diagnostic accuracy. Alternatively, or in concert with this approach, evaluating high‐risk populations (eg, patients with rapid eye movement behavior disorder or LRRK2 mutations) would enrich the sample for cases with underlying PD. Ultimately, the role of preclinical detection of PD will be determined by the ability of emerging therapies to influence clinical outcomes. As such, implementation of large‐scale screening strategies awaits the arrival of clearly safe and effective therapies that address the underlying pathogenesis of PD. Future research will establish more definitive biomarkers capable of revealing the presence of disease in advance of SNc involvement with the promise of the potential for introducing disease‐modifying therapy even before the development of evidence of dopamine deficiency. © 2012 Movement Disorder Society |
| Author | Siderowf, Andrew Lang, Anthony E. |
| Author_xml | – sequence: 1 givenname: Andrew surname: Siderowf fullname: Siderowf, Andrew email: Andrew.siderowf@uphs.upenn.edu organization: Parkinson's Disease and Mov Disord. Center, Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA – sequence: 2 givenname: Anthony E. surname: Lang fullname: Lang, Anthony E. organization: Moverment Disorders Center and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital and the Department of Medicine, University of Toronto, Toronto, Ontario, Canada |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/22508279$$D View this record in MEDLINE/PubMed |
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| Notes | Full financial disclosures and author roles may be found in the online version of this article. ArticleID:MDS24954 Relevant conflicts of interest/financial disclosures: Andrew Siderowf is supported by a Morris K. Udall Parkinson's Disease Research Center of Excellence grant from NINDS (NS-053488) and has been supported by SAP4100027296, a health research grant awarded by the Department of Health of the Commonwealth of Pennsylvania from the Tobacco Master Settlement Agreement under Act 2001-77; has received consulting fees from Teva Neuroscience, Ipsen Pharmaceuticals, Schering-Plough, Merck Serono, and General Electric; has received speaking honoraria from Teva Neuroscience; and has received research support from Avid Radiopharmaceuticals. Anthony Lang has served as an adviser for Abbott, Allon Therapeutics, Astra Zenica, Avanir Pharmaceuticals, Biovail, Boerhinger-Ingelheim, Cephalon, Ceregene, Eisai, GSK, Lundbeck A/S, Medtronic, Merck Serono, Novartis, Santhera, Solvay, and Teva; has received grants from Canadian Institutes of Health Research, Dystonia Medical Research Foundation, Michael J. Fox Foundation, National Parkinson Foundation, and Ontario Problem Gambling Research Centre; has received publishing royalties from Saunders, Wiley-Blackwell, Johns Hopkins Press, and Cambridge University Press; and has served as an expert witness in cases related to the welding industry. istex:B586494841D9C771E5B50B0803AF4C3147F27BA3 This article is partially adapted from the following publications: Siderowf A, Stern MB. Premotor Parkinson's disease: clinical features, detection, and prospects for treatment. Ann Neurol. 2008; 64:S139-S147; Lang AE. A critical appraisal of the premotor symptoms of Parkinson's disease: potential usefulness in early diagnosis and design of neuroprotective trials. Mov Disord. 2011;26:775-783. ark:/67375/WNG-PJ81K619-Z Mov Disord. 2011;26:775–783. 2008; 64:S139–S147; Lang AE. A critical appraisal of the premotor symptoms of Parkinson's disease: potential usefulness in early diagnosis and design of neuroprotective trials. This article is partially adapted from the following publications: Siderowf A, Stern MB. Premotor Parkinson's disease: clinical features, detection, and prospects for treatment. Andrew Siderowf is supported by a Morris K. Udall Parkinson's Disease Research Center of Excellence grant from NINDS (NS‐053488) and has been supported by SAP4100027296, a health research grant awarded by the Department of Health of the Commonwealth of Pennsylvania from the Tobacco Master Settlement Agreement under Act 2001‐77; has received consulting fees from Teva Neuroscience, Ipsen Pharmaceuticals, Schering‐Plough, Merck Serono, and General Electric; has received speaking honoraria from Teva Neuroscience; and has received research support from Avid Radiopharmaceuticals. Anthony Lang has served as an adviser for Abbott, Allon Therapeutics, Astra Zenica, Avanir Pharmaceuticals, Biovail, Boerhinger‐Ingelheim, Cephalon, Ceregene, Eisai, GSK, Lundbeck A/S, Medtronic, Merck Serono, Novartis, Santhera, Solvay, and Teva; has received grants from Canadian Institutes of Health Research, Dystonia Medical Research Foundation, Michael J. Fox Foundation, National Parkinson Foundation, and Ontario Problem Gambling Research Centre; has received publishing royalties from Saunders, Wiley‐Blackwell, Johns Hopkins Press, and Cambridge University Press; and has served as an expert witness in cases related to the welding industry. Relevant conflicts of interest/financial disclosures Ann Neurol. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
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| Snippet | Parkinson's disease (PD) has a prodromal phase during which nonmotor clinical features as well as physiological abnormalities may be present. These premotor... |
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| SubjectTerms | early detection Early Diagnosis Humans Motor Neurons - pathology Parkinson Disease - classification Parkinson Disease - diagnosis Parkinson Disease - etiology Parkinson Disease - genetics Parkinson Disease - therapy Parkinson's disease sensitivity specificity |
| Title | Premotor Parkinson's disease: Concepts and definitions |
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