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Diagnosis and differential diagnosis of Parkinson disease

Kelvin L Chou, MD
Section Editor
Howard I Hurtig, MD
Deputy Editor
John F Dashe, MD, PhD


Parkinson disease (PD) or Lewy body parkinsonism, is a chronic, progressive neurodegenerative disorder characterized by any combination of four cardinal signs: bradykinesia, rest tremor, rigidity, and postural instability (present in later stages of disease). Because no diagnostic tests have been developed to distinguish PD from other forms of parkinsonism in vivo, PD remains a clinical diagnosis, based on the clinician's ability to recognize its characteristic signs and associated symptoms, especially in the early stages. An accurate clinical diagnosis is fundamental to the expectation that pharmacotherapy of PD will be effective. In general, the other forms of parkinsonism tend to respond poorly to antiparkinson drugs.

This topic will review the diagnosis and differential diagnosis of PD. Other aspects of PD are discussed separately. (See "Etiology and pathogenesis of Parkinson disease" and "Clinical manifestations of Parkinson disease" and "Pharmacologic treatment of Parkinson disease" and "Nonpharmacologic management of Parkinson disease" and "Motor fluctuations and dyskinesia in Parkinson disease" and "Device-assisted and surgical treatments for Parkinson disease".)


The diagnosis of PD during life is based upon its distinctive clinical features discerned from the history and neurologic examination. At a minimum, bradykinesia plus either tremor or rigidity must be present in order to consider the diagnosis of PD [1,2]. In addition, an unequivocal, beneficial response to dopaminergic therapy is an important supportive feature of the diagnosis, while the absence of an observable response to high-dose levodopa therapy (>1000 mg daily) in patients with at least a moderate severity of parkinsonism makes the diagnosis of PD extremely unlikely. Other clinical features that are supportive of the diagnosis are unilateral onset, presence of a rest tremor, and a persistent asymmetry throughout the course of the disease, with the side of onset most affected [3]. (See "Clinical manifestations of Parkinson disease".)

Postural instability is also a feature of PD but usually does not appear until later in the course of the disease. Thus, patients with parkinsonian signs who exhibit postural instability early in the course of the illness most likely have another parkinsonian syndrome.

There are no physiologic tests or blood tests for confirming the clinical diagnosis of PD, and neurodiagnostic testing with CT or MRI is usually unrevealing. Nevertheless, MRI is reasonable to perform in every patient to exclude rare, unexpected mimics of PD, such as stroke or hydrocephalus. While the true "gold standard" for a definitive diagnosis is neuropathologic examination, the "gold standard" for a clinical diagnosis according to criteria from the Movement Disorder Society is an expert clinician. (See 'Diagnostic criteria' below.)

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Literature review current through: Nov 2017. | This topic last updated: Jul 05, 2017.
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  1. Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord 2015; 30:1591.
  2. Gibb WR, Lees AJ. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. J Neurol Neurosurg Psychiatry 1988; 51:745.
  3. 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.
  4. Goetz CG, Tilley BC, Shaftman SR, et al. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord 2008; 23:2129.
  5. Colosimo C, Pezzella FR. The symptomatic treatment of multiple system atrophy. Eur J Neurol 2002; 9:195.
  6. Zijlmans JC, Katzenschlager R, Daniel SE, Lees AJ. The L-dopa response in vascular parkinsonism. J Neurol Neurosurg Psychiatry 2004; 75:545.
  7. Rossi P, Colosimo C, Moro E, et al. Acute challenge with apomorphine and levodopa in Parkinsonism. Eur Neurol 2000; 43:95.
  8. Merello M, Nouzeilles MI, Arce GP, Leiguarda R. Accuracy of acute levodopa challenge for clinical prediction of sustained long-term levodopa response as a major criterion for idiopathic Parkinson's disease diagnosis. Mov Disord 2002; 17:795.
  9. Suchowersky O, Reich S, Perlmutter J, et al. Practice Parameter: diagnosis and prognosis of new onset Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006; 66:968.
  10. Clarke CE, Davies P. Systematic review of acute levodopa and apomorphine challenge tests in the diagnosis of idiopathic Parkinson's disease. J Neurol Neurosurg Psychiatry 2000; 69:590.
  11. Rizzo G, Copetti M, Arcuti S, et al. Accuracy of clinical diagnosis of Parkinson disease: A systematic review and meta-analysis. Neurology 2016; 86:566.
  12. Marras C, McDermott MP, Rochon PA, et al. Survival in Parkinson disease: thirteen-year follow-up of the DATATOP cohort. Neurology 2005; 64:87.
  13. Adler CH, Beach TG, Hentz JG, et al. Low clinical diagnostic accuracy of early vs advanced Parkinson disease: clinicopathologic study. Neurology 2014; 83:406.
  14. Perlmutter JS, Norris SA. Neuroimaging biomarkers for Parkinson disease: facts and fantasy. Ann Neurol 2014; 76:769.
  15. Stoessl AJ, Lehericy S, Strafella AP. Imaging insights into basal ganglia function, Parkinson's disease, and dystonia. Lancet 2014; 384:532.
  16. Stern MB, Braffman BH, Skolnick BE, et al. Magnetic resonance imaging in Parkinson's disease and parkinsonian syndromes. Neurology 1989; 39:1524.
  17. Asato R, Akiguchi I, Masunaga S, Hashimoto N. Magnetic resonance imaging distinguishes progressive supranuclear palsy from multiple system atrophy. J Neural Transm (Vienna) 2000; 107:1427.
  18. Konagaya M, Konagaya Y, Iida M. Clinical and magnetic resonance imaging study of extrapyramidal symptoms in multiple system atrophy. J Neurol Neurosurg Psychiatry 1994; 57:1528.
  19. Yekhlef F, Ballan G, Macia F, et al. Routine MRI for the differential diagnosis of Parkinson's disease, MSA, PSP, and CBD. J Neural Transm (Vienna) 2003; 110:151.
  20. Tolosa E, Wenning G, Poewe W. The diagnosis of Parkinson's disease. Lancet Neurol 2006; 5:75.
  21. Seppi K, Schocke MF. An update on conventional and advanced magnetic resonance imaging techniques in the differential diagnosis of neurodegenerative parkinsonism. Curr Opin Neurol 2005; 18:370.
  22. Vaillancourt DE, Spraker MB, Prodoehl J, et al. High-resolution diffusion tensor imaging in the substantia nigra of de novo Parkinson disease. Neurology 2009; 72:1378.
  23. Wang JJ, Lin WY, Lu CS, et al. Parkinson disease: diagnostic utility of diffusion kurtosis imaging. Radiology 2011; 261:210.
  24. Seppi K, Poewe W. Brain magnetic resonance imaging techniques in the diagnosis of parkinsonian syndromes. Neuroimaging Clin N Am 2010; 20:29.
  25. Mahlknecht P, Hotter A, Hussl A, et al. Significance of MRI in diagnosis and differential diagnosis of Parkinson's disease. Neurodegener Dis 2010; 7:300.
  26. Lehéricy S, Sharman MA, Dos Santos CL, et al. Magnetic resonance imaging of the substantia nigra in Parkinson's disease. Mov Disord 2012; 27:822.
  27. Cochrane CJ, Ebmeier KP. Diffusion tensor imaging in parkinsonian syndromes: a systematic review and meta-analysis. Neurology 2013; 80:857.
  28. Cosottini M, Frosini D, Pesaresi I, et al. MR imaging of the substantia nigra at 7 T enables diagnosis of Parkinson disease. Radiology 2014; 271:831.
  29. Wu G, Shen YJ, Huang MH, et al. Proton MR Spectroscopy for Monitoring Pathologic Changes in the Substantia Nigra and Globus Pallidus in Parkinson Disease. AJR Am J Roentgenol 2016; 206:385.
  30. Mazuel L, Chassain C, Jean B, et al. Proton MR Spectroscopy for Diagnosis and Evaluation of Treatment Efficacy in Parkinson Disease. Radiology 2016; 278:505.
  31. Reiter E, Mueller C, Pinter B, et al. Dorsolateral nigral hyperintensity on 3.0T susceptibility-weighted imaging in neurodegenerative Parkinsonism. Mov Disord 2015; 30:1068.
  32. Mahlknecht P, Krismer F, Poewe W, Seppi K. Meta-analysis of dorsolateral nigral hyperintensity on magnetic resonance imaging as a marker for Parkinson's disease. Mov Disord 2017; 32:619.
  33. Stoessl AJ, Martin WW, McKeown MJ, Sossi V. Advances in imaging in Parkinson's disease. Lancet Neurol 2011; 10:987.
  34. Kägi G, Bhatia KP, Tolosa E. The role of DAT-SPECT in movement disorders. J Neurol Neurosurg Psychiatry 2010; 81:5.
  35. de la Fuente-Fernández R. Role of DaTSCAN and clinical diagnosis in Parkinson disease. Neurology 2012; 78:696.
  36. Perlmutter JS, Eidelberg D. To scan or not to scan: DaT is the question. Neurology 2012; 78:688.
  37. Tolosa E, Borght TV, Moreno E, DaTSCAN Clinically Uncertain Parkinsonian Syndromes Study Group. Accuracy of DaTSCAN (123I-Ioflupane) SPECT in diagnosis of patients with clinically uncertain parkinsonism: 2-year follow-up of an open-label study. Mov Disord 2007; 22:2346.
  38. Teune LK, Bartels AL, de Jong BM, et al. Typical cerebral metabolic patterns in neurodegenerative brain diseases. Mov Disord 2010; 25:2395.
  39. Pavese N. PET studies in Parkinson's disease motor and cognitive dysfunction. Parkinsonism Relat Disord 2012; 18 Suppl 1:S96.
  40. Hellwig S, Amtage F, Kreft A, et al. [¹⁸F]FDG-PET is superior to [¹²³I]IBZM-SPECT for the differential diagnosis of parkinsonism. Neurology 2012; 79:1314.
  41. Eckert T, Barnes A, Dhawan V, et al. FDG PET in the differential diagnosis of parkinsonian disorders. Neuroimage 2005; 26:912.
  42. Tang CC, Poston KL, Eckert T, et al. Differential diagnosis of parkinsonism: a metabolic imaging study using pattern analysis. Lancet Neurol 2010; 9:149.
  43. Stern MB. Transcranial ultrasound in Parkinson's disease. Lancet Neurol 2008; 7:376.
  44. Berg D, Godau J, Walter U. Transcranial sonography in movement disorders. Lancet Neurol 2008; 7:1044.
  45. Gaenslen A, Unmuth B, Godau J, et al. The specificity and sensitivity of transcranial ultrasound in the differential diagnosis of Parkinson's disease: a prospective blinded study. Lancet Neurol 2008; 7:417.
  46. Walter U, Niehaus L, Probst T, et al. Brain parenchyma sonography discriminates Parkinson's disease and atypical parkinsonian syndromes. Neurology 2003; 60:74.
  47. Stockner H, Schwingenschuh P, Djamshidian A, et al. Is transcranial sonography useful to distinguish scans without evidence of dopaminergic deficit patients from Parkinson's disease? Mov Disord 2012; 27:1182.
  48. 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.
  49. 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.
  50. Montgomery EB Jr. Predictors of Parkinson's disease--not quite sound. Mov Disord 2013; 28:413.
  51. Deeb J, Shah M, Muhammed N, et al. A basic smell test is as sensitive as a dopamine transporter scan: comparison of olfaction, taste and DaTSCAN in the diagnosis of Parkinson's disease. QJM 2010; 103:941.
  52. Wenning GK, Shephard B, Hawkes C, et al. Olfactory function in atypical parkinsonian syndromes. Acta Neurol Scand 1995; 91:247.
  53. Müller A, Müngersdorf M, Reichmann H, et al. Olfactory function in Parkinsonian syndromes. J Clin Neurosci 2002; 9:521.
  54. Kikuchi A, Baba T, Hasegawa T, et al. Differentiating Parkinson's disease from multiple system atrophy by [123I] meta-iodobenzylguanidine myocardial scintigraphy and olfactory test. Parkinsonism Relat Disord 2011; 17:698.
  55. Berardelli A, Wenning GK, Antonini A, et al. EFNS/MDS-ES/ENS [corrected] recommendations for the diagnosis of Parkinson's disease. Eur J Neurol 2013; 20:16.
  56. Katzenschlager R, Lees AJ. Olfaction and Parkinson's syndromes: its role in differential diagnosis. Curr Opin Neurol 2004; 17:417.
  57. Katzenschlager R, Zijlmans J, Evans A, et al. Olfactory function distinguishes vascular parkinsonism from Parkinson's disease. J Neurol Neurosurg Psychiatry 2004; 75:1749.
  58. Orimo S, Suzuki M, Inaba A, Mizusawa H. 123I-MIBG myocardial scintigraphy for differentiating Parkinson's disease from other neurodegenerative parkinsonism: a systematic review and meta-analysis. Parkinsonism Relat Disord 2012; 18:494.
  59. Ahlskog JE. Diagnosis and differential diagnosis of Parkinson's disease and parkinsonism. Parkinsonism Relat Disord 2000; 7:63.
  60. Jankovic J, Schwartz KS, Ondo W. Re-emergent tremor of Parkinson's disease. J Neurol Neurosurg Psychiatry 1999; 67:646.
  61. Louis ED, Levy G, Côte LJ, et al. Clinical correlates of action tremor in Parkinson disease. Arch Neurol 2001; 58:1630.
  62. Jain S, Lo SE, Louis ED. Common misdiagnosis of a common neurological disorder: how are we misdiagnosing essential tremor? Arch Neurol 2006; 63:1100.
  63. Schneider SA, Edwards MJ, Mir P, et al. Patients with adult-onset dystonic tremor resembling parkinsonian tremor have scans without evidence of dopaminergic deficit (SWEDDs). Mov Disord 2007; 22:2210.
  64. Cilia R, Reale C, Castagna A, et al. Novel DYT11 gene mutation in patients without dopaminergic deficit (SWEDD) screened for dystonia. Neurology 2014; 83:1155.
  65. Bain PG. Dystonic tremor presenting as parkinsonism: long-term follow-up of SWEDDs. Neurology 2009; 72:1443.
  66. Marek K, Seibyl J, Eberly S, et al. Longitudinal follow-up of SWEDD subjects in the PRECEPT Study. Neurology 2014; 82:1791.
  67. Erro R, Schneider SA, Stamelou M, et al. What do patients with scans without evidence of dopaminergic deficit (SWEDD) have? New evidence and continuing controversies. J Neurol Neurosurg Psychiatry 2016; 87:319.
  68. McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology 2017; 89:88.
  69. Boeve BF, Dickson DW, Duda JE, et al. Arguing against the proposed definition changes of PD. Mov Disord 2016; 31:1619.
  70. Manyam BV, Walters AS, Narla KR. Bilateral striopallidodentate calcinosis: clinical characteristics of patients seen in a registry. Mov Disord 2001; 16:258.
  71. Nicolas G, Pottier C, Charbonnier C, et al. Phenotypic spectrum of probable and genetically-confirmed idiopathic basal ganglia calcification. Brain 2013; 136:3395.
  72. Ellie E, Julien J, Ferrer X. Familial idiopathic striopallidodentate calcifications. Neurology 1989; 39:381.
  73. Tadic V, Westenberger A, Domingo A, et al. Primary familial brain calcification with known gene mutations: a systematic review and challenges of phenotypic characterization. JAMA Neurol 2015; 72:460.
  74. Wang C, Li Y, Shi L, et al. Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis. Nat Genet 2012; 44:254.
  75. Nicolas G, Pottier C, Maltête D, et al. Mutation of the PDGFRB gene as a cause of idiopathic basal ganglia calcification. Neurology 2013; 80:181.
  76. Keller A, Westenberger A, Sobrido MJ, et al. Mutations in the gene encoding PDGF-B cause brain calcifications in humans and mice. Nat Genet 2013; 45:1077.
  77. Keogh MJ, Pyle A, Daud D, et al. Clinical heterogeneity of primary familial brain calcification due to a novel mutation in PDGFB. Neurology 2015; 84:1818.
  78. Legati A, Giovannini D, Nicolas G, et al. Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. Nat Genet 2015; 47:579.
  79. Geschwind DH, Loginov M, Stern JM. Identification of a locus on chromosome 14q for idiopathic basal ganglia calcification (Fahr disease). Am J Hum Genet 1999; 65:764.
  80. Volpato CB, De Grandi A, Buffone E, et al. 2q37 as a susceptibility locus for idiopathic basal ganglia calcification (IBGC) in a large South Tyrolean family. J Mol Neurosci 2009; 39:346.
  81. Manyam BV. What is and what is not 'Fahr's disease'. Parkinsonism Relat Disord 2005; 11:73.
  82. Koller WC, Cochran JW, Klawans HL. Calcification of the basal ganglia: computerized tomography and clinical correlation. Neurology 1979; 29:328.
  83. Harrington MG, Macpherson P, McIntosh WB, et al. The significance of the incidental finding of basal ganglia calcification on computed tomography. J Neurol Neurosurg Psychiatry 1981; 44:1168.
  84. Förstl H, Krumm B, Eden S, Kohlmeyer K. Neurological disorders in 166 patients with basal ganglia calcification: a statistical evaluation. J Neurol 1992; 239:36.
  85. Kalra S, Grosset DG, Benamer HT. Differentiating vascular parkinsonism from idiopathic Parkinson's disease: a systematic review. Mov Disord 2010; 25:149.
  86. Vale TC, Caramelli P, Cardoso F. Clinicoradiological comparison between vascular parkinsonism and Parkinson's disease. J Neurol Neurosurg Psychiatry 2015; 86:547.
  87. Vizcarra JA, Lang AE, Sethi KD, Espay AJ. Vascular Parkinsonism: deconstructing a syndrome. Mov Disord 2015; 30:886.
  88. van der Holst HM, van Uden IW, Tuladhar AM, et al. Cerebral small vessel disease and incident parkinsonism: The RUN DMC study. Neurology 2015; 85:1569.
  89. Reider-Groswasser I, Bornstein NM, Korczyn AD. Parkinsonism in patients with lucanar infarcts of the basal ganglia. Eur Neurol 1995; 35:46.
  90. Peralta C, Werner P, Holl B, et al. Parkinsonism following striatal infarcts: incidence in a prospective stroke unit cohort. J Neural Transm (Vienna) 2004; 111:1473.
  91. Buchman AS, Leurgans SE, Nag S, et al. Cerebrovascular disease pathology and parkinsonian signs in old age. Stroke 2011; 42:3183.
  92. Mena MA, de Yébenes JG. Drug-induced parkinsonism. Expert Opin Drug Saf 2006; 5:759.
  93. Savica R, Grossardt BR, Bower JH, et al. Incidence and time trends of drug-induced parkinsonism: A 30-year population-based study. Mov Disord 2017; 32:227.
  94. Hardie RJ, Lees AJ. Neuroleptic-induced Parkinson's syndrome: clinical features and results of treatment with levodopa. J Neurol Neurosurg Psychiatry 1988; 51:850.
  95. Jankovic J, Casabona J. Coexistent tardive dyskinesia and parkinsonism. Clin Neuropharmacol 1987; 10:511.
  96. Erro R, Bhatia KP, Tinazzi M. Parkinsonism following neuroleptic exposure: A double-hit hypothesis? Mov Disord 2015; 30:780.
  97. Foubert-Samier A, Helmer C, Perez F, et al. Past exposure to neuroleptic drugs and risk of Parkinson disease in an elderly cohort. Neurology 2012; 79:1615.