Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-745bb68f8f-d8cs5 Total loading time: 0 Render date: 2025-01-09T11:21:17.980Z Has data issue: false hasContentIssue false

Chapter 17 - Diagnosis of Parkinson’s Disease

A Critical Reappraisal of UK Brain Bank and MDS Diagnostic Criteria

from Section 2: - Hypokinetic Movement Disorders

Published online by Cambridge University Press:  07 January 2025

By
Christian R. Baumann ,
Kathrin Brockmann  and
Daniela Berg
Edited by
Erik Ch. Wolters  and
Christian R. Baumann
Erik Ch. Wolters
Affiliation:
Universität Zürich
Christian R. Baumann
Affiliation:
Universität Zürich
Get access

Summary

The clinical and pathologic hallmarks of Parkinson’s disease (PD) are motor parkinsonism due to underlying progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta accompanied by an accumulation of intracytoplasmic protein inclusions known as Lewy bodies and Lewy neurites. The diagnostic criteria/guidelines based on the UK Parkinson’s Disease Society Brain Bank clinical diagnostic criteria have guided clinicians and researchers in the diagnosis of PD for many decades. This chapter discusses whether this description represents our current understanding of PD, and why it is time to integrate new research findings and accommodate our definition and diagnostic criteria of PD, such as Parkinson-associated non-motor symptoms, genetics, biomarkers, imaging findings, or heterogeneity of phenotypes and underlying molecular mechanisms. In 2015, the International Parkinson and Movement Disorder Society published clinical diagnostic criteria for Parkinson’s disease, which were designed specifically for use in research but also as a general guide to clinical diagnosis of PD. These criteria and some of their limitations are also discussed.

Keywords

Parkinson’s diseasediagnostic criterianon-motor symptomsgeneticsbiomarkersneuroimaging
Type
Chapter
Information
International Compendium of Movement Disorders , pp. 202 - 211
Publisher: Cambridge University Press
Print publication year: 2025

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Hughes, AJ, Daniel, SE, Kilford, L, Lees, AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992;55:181–184.CrossRefGoogle ScholarPubMed
Postuma, RB, Berg, D, Stern, M, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord 2015;30:1591–1601.CrossRefGoogle ScholarPubMed
Hughes, AJ, Daniel, SE, Lees, AJ. Improved accuracy of clinical diagnosis of Lewy body Parkinson’s disease. Neurology 2001;57:1497–1499.CrossRefGoogle ScholarPubMed
Buchman, AS, Shulman, JM, Nag, S, et al. Nigral pathology and parkinsonian signs in elders without Parkinson disease. Ann Neurol 2012;71:258–266.CrossRefGoogle ScholarPubMed
Lost, D, Tang, MX, Schupf, N, Mayeux, R. Functional correlates and prevalence of mild parkinsonian signs in a community population of older people. ArchNeurol 2005;62:297–302.Google Scholar
Buchman, AS, Nag, S, Shulman, JM, et al. Locus coeruleus neuron density and parkinsonism in older adults without Parkinson’s disease. Mov Disord 2012;27:1625–1631.CrossRefGoogle ScholarPubMed
Adler, CH, Connor, DJ, Hentz, JG, et al. Incidental Lewy body disease: clinical comparison to a control cohort. Mov Disord 2010;25:642–646.CrossRefGoogle ScholarPubMed
Ross, GW, Petrovitch, H, Abbott, RD, et al. Parkinsonian signs and substantia nigra neuron density in decendents elders without PD. Ann Neurol 2004;56:532–539.CrossRefGoogle ScholarPubMed
Bennett, DA, Beckett, LA, Murray, AM, et al. Prevalence of parkinsonian signs and associated mortality in a community population of older people. N Engl J Med 1996;334:71–76.CrossRefGoogle Scholar
Fearnley, JM, Lees, AJ. Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain 1991;114:2283–2301.CrossRefGoogle ScholarPubMed
Bezard, E, Gross, CE, Brotchie, JM. Presymptomatic compensation in Parkinson’s disease is not dopamine-mediated. Trends Neurosci 2003;26:215–221.CrossRefGoogle Scholar
Postuma, RB, Lang, AE, Gagnon, JF, Pelletier, A, Montplaisir, JY. How does parkinsonism start? Prodromal parkinsonism motor changes in idiopathic REM sleep behaviour disorder. Brain 2012;135:1860–1870.CrossRefGoogle ScholarPubMed
Mirelman, A, Gurevich, T, Giladi, N, et al. Gait alterations in healthy carriers of the LRRK2 G2019S mutation. Ann Neurol 2011;69(1):193–197.CrossRefGoogle ScholarPubMed
Maetzler, W, Mancini, M, Liepelt-Scarfone, I, et al. Impaired trunk stability in individuals at high risk for Parkinson’s disease. PLoS One 2012;7:e32240.CrossRefGoogle ScholarPubMed
Chaudhuri, KR, Schapira, AH. Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol 2009;8:464–474.CrossRefGoogle Scholar
Ross, GW, Petrovitch, H, Abbott, RD, et al. Association of olfactory dysfunction with risk for future Parkinson’s disease. Ann Neurol 2008;63:167–173.CrossRefGoogle ScholarPubMed
Tolosa, E, Compta, Y, Gaig, C. The premotor phase of Parkinson’s disease. Parkinsonism Relat Disord 2007;13(Suppl):S2–7.CrossRefGoogle ScholarPubMed
Leentjens, AF, Van den Akker, M, Metsemakers, JF, Lousberg, R, Verhey, FR. Higher incidence of depression preceding the onset of Parkinson’s disease: a register study. Mov Disord 2003;18:414–418.CrossRefGoogle ScholarPubMed
Iranzo, A, Molinuevo, JL, Santamaria, J, et al. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol 2006;5:572–577.CrossRefGoogle Scholar
Liepelt, I, Behnke, S, Schweitzer, K, et al. Pre-motor signs of PD are related to SN hyperechogenicity assessed by TCS in an elderly population. Neurobiol Aging 2011;32:1599–1606.CrossRefGoogle Scholar
Berg, D, Poewe, W. Can we define ‘pre-motor’ Parkinson’s disease? Mov Disord 2012;27:595–596.CrossRefGoogle ScholarPubMed
Berg, D, Postuma, RB, Adler, CH, et al. MDS research criteria for prodromal Parkinson’s disease. Mov Disord 2015;30:1600–1611.CrossRefGoogle ScholarPubMed
Spillantini, MG, Schmidt, ML, Lee, VM, Trojanowski, JQ, Jakes, R, Goedert, M. Alpha-synuclein in Lewy bodies. Nature 1997;388:839–840.CrossRefGoogle ScholarPubMed
Lesage, S, Brice, A. Parkinson’s disease: from monogenic forms to genetic susceptibility factors. Hum Molec Genet 2009;18(R1):R48–59.CrossRefGoogle ScholarPubMed
Healy, DG, Falchi, M, O’Sullivan, SS, et al. Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson’s disease: a case–control study. Lancet Neurol 2008;7:583–590.CrossRefGoogle ScholarPubMed
Brockmann, K, Groger, A, Di Santo, A, et al. Clinical and brain imaging characteristics in leucine-rich repeat kinase 2-associated PD and asymptomatic mutation carriers. Mov Disord 2011;26:2335–2342.CrossRefGoogle ScholarPubMed
Hasegawa, K, Stoessl, AJ, Yokoyama, T, et al. Familial parkinsonism: study of original Sagamihara PARK8 (I2020T) kindred with variable clinicopathologic outcomes. Parkinsonism Relat Disord 2009;15:300–306.CrossRefGoogle ScholarPubMed
Lücking, CB, Dürr, A, Bonifati, V, et al. Association between early-onset Parkinson’s disease and mutations in the parkin gene. N Engl J Med 2000;342:1560–1567.CrossRefGoogle ScholarPubMed
Valente, EM, Bentivoglio, AR, Dixon, PH, et al. Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human chromosome 1p35-p36. Am J Hum Genet 2001;6:895–900.CrossRefGoogle Scholar
van de Warrenburg, BP, Lammens, M, Lücking, CB, et al. Clinical and pathologic abnormalities in a family with parkinsonism and parkin gene mutations. Neurology 2001;56:555–557.CrossRefGoogle Scholar
Farrer, M, Chan, P, Chen, R, et al. Lewy bodies and parkinsonism in families with parkin mutations. Ann Neurol 2001;50:293–300.CrossRefGoogle ScholarPubMed
Samaranch, L, Lorenzo-Betancor, O, Arbelo, JM, et al. PINK1-linked parkinsonism is associated with Lewy body pathology. Brain 2010;133:1128–1142.CrossRefGoogle ScholarPubMed
Park, J, Lee, SB, Lee, S, Kim, Y, Song, S, Kim, S, et al. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature 2006;441:1157–1161.CrossRefGoogle ScholarPubMed
International Parkinson Disease Genome Consortium; Nalls, MA, Plagnol, V, Hernandez, DG, et al. Imputation of sequence variants for identification of genetic risks for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet 2011;377:641–649.Google ScholarPubMed
Sharma, M, Ioannidis, JP, Aasly, JO, et al. Large-scale replication and heterogeneity in Parkinson disease genetic loci. Neurology 2012;79:659–667.CrossRefGoogle ScholarPubMed
Simon-Sanchez, J, Schulte, C, Bras, JM, et al. Genome-wide association study reveals genetic risk underlying Parkinson’s disease. Nature Genet 2009;41:1308–1312.CrossRefGoogle ScholarPubMed
Sidransky, E, Nalls, MA, Aasly, JO, et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson’s disease. N Engl J Med 2009;361:1651–1661.CrossRefGoogle ScholarPubMed
Brockmann, K, Schulte, C, Hauser, AK, et al. SNCA: major genetic modifier of age at onset of Parkinson’s disease. Mov Disord 2013;28(9):1217–1221.CrossRefGoogle ScholarPubMed
Ritz, B, Rhodes, SL, Bordelon, Y, Bronstein, J. Alpha-synuclein genetic variants predict faster motor symptom progression in idiopathic Parkinson disease. PLoS One 2012;7:e36199.CrossRefGoogle ScholarPubMed
Hardy, J. Genetic analysis of pathways to Parkinson disease. Neuron 2010;68:201–206.CrossRefGoogle ScholarPubMed
Stoessl, AJ. Neuroimaging in Parkinson’s disease. Neurotherapeutics 2011;8:72–81.CrossRefGoogle ScholarPubMed
Stoessl, AJ, Martin, WW, McKeown, MJ, Sossi, V. Advances in imaging in Parkinson’s disease. Lancet Neurol 2011;10:987–1001.CrossRefGoogle ScholarPubMed
Piccini, P, Burn, DJ, Ceravolo, R, Maraganore, D, Brooks, DJ. The role of inheritance in sporadic Parkinson’s disease: evidence from a longitudinal study of dopaminergic function in twins. Ann Neurol 1999;45:577–582.3.0.CO;2-O>CrossRefGoogle ScholarPubMed
Cho, ZH, Oh, SH, Kim, JM, et al. Direct visualization of Parkinson’s disease by in vivo human brain imaging using 7.0T magnetic resonance imaging. Mov Disord 2011;26:713–718.CrossRefGoogle ScholarPubMed
Kwon, DH, Kim, JM, Oh, SH, et al. Seven-Tesla magnetic resonance images of the substantia nigra in Parkinson disease. Ann Neurol 2012;71:267–277.CrossRefGoogle ScholarPubMed
Berg, D, Godau, J, Walter, U. Transcranial sonography in movement disorders. Lancet Neurol 2008;7:1044–1055.CrossRefGoogle ScholarPubMed
Berg, D, Seppi, K, Behnke, S, et al. Enlarged substantia nigra hyperechogenicity and risk for Parkinson disease: a 37-month 3-center study of 1847 older persons. Arch Neurol 2011;68:932–937.CrossRefGoogle ScholarPubMed
Brockmann, K, Hagenah, J. TCS in monogenic forms of Parkinson’s disease. Int Rev Neurobiol 2010;90:157–164.CrossRefGoogle ScholarPubMed
Berg, D, Behnke, S, Seppi, K, et al. Enlarged hyperechogenic substantia nigra as a risk marker for Parkinson’s disease. Mov Disord 2013;28:216–219.CrossRefGoogle ScholarPubMed
Goedert, M, Spillantini, MG, Del Tredici, K, Braak, H. 100 years of Lewy pathology. Nat Rev Neurol 2013;9:13–24.CrossRefGoogle ScholarPubMed
Braak, H, Del Tredici, K, Rub, U, et al. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 2003;24:197–211.CrossRefGoogle ScholarPubMed
Buchman, AS, Shulman, JM, Nag, S, et al. Nigral pathology and parkinsonian signs in elders without Parkinson disease. Ann Neurol 2012;71:258–266.CrossRefGoogle ScholarPubMed
Perez, F, Helmer, C, Dartigues, JF, Auriacombe, S, Tison, F. A 15-year population-based cohort study of the incidence of Parkinson’s disease and dementia with Lewy bodies in an elderly French cohort. J Neurol Neurosurg Psychiatry 2010;81:742–746.CrossRefGoogle Scholar
Olanow, CW, Perl, DP, DeMartino, GN, McNaught, KS. Lewy-body formation is an aggresome-related process: a hypothesis. Lancet Neurol 2004;3:496–503.CrossRefGoogle Scholar
Milber, JM, Noorigian, JV, Morley, JF, et al. Lewy pathology is not the first sign of degeneration in vulnerable neurons in Parkinson disease. Neurology 2012;79:2307–2314.CrossRefGoogle Scholar
Kramer, ML, Schulz-Schaeffer, WJ. Presynaptic alpha-synuclein aggregates, not Lewy bodies, cause neurodegeneration in dementia with Lewy bodies. J Neurosci 2007;27:1405–1410.CrossRefGoogle Scholar
Schulz-Schaeffer, WJ. The synaptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies, Parkinson’s disease and Parkinson’s disease dementia. Acta Neuropathol 2010;120:131–143.CrossRefGoogle ScholarPubMed
Hattori, N, Shimura, H, Kubo, S, et al. Autosomal recessive juvenile parkinsonism: a key to understanding nigral degeneration in sporadic Parkinson’s disease. Neuropathology 2000;20(Suppl):S85–90.CrossRefGoogle ScholarPubMed
Martí-Massó, JF, Ruiz-Martinez, J, Bolano, MJ, et al. Neuropathology of Parkinson’s disease with the R1441G mutation in LRRK2. Mov Disord 2009;24:1998–2001.CrossRefGoogle ScholarPubMed
Kordower, JH, Chu, Y, Hauser, RA, Freeman, TB, Olanow, CW. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson’s disease. Nat Med 2008;14:504–506.CrossRefGoogle ScholarPubMed
Luk, KC, Kehm, V, Carroll, J, et al. Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 2012;338:949–953.CrossRefGoogle ScholarPubMed
Berg, D, Adler, CH, Bloem, BR, et al. Movement disorder society criteria for clinically established early Parkinson’s disease. Mov Disord 2018;33(10):1643–1646.CrossRefGoogle ScholarPubMed
Brockmann, K, Berg, D. Diagnosis of Parkinson’s disease. In: Wolters, ECh, Baumann, CR, eds. Parkinson Disease and Other Movement Disorders. Motor Behavioural Disorders and Behavioural Motor Disorders. Amsterdam: VU University Press, 2014; 229–242.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×