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Potential impact of self-perceived prodromal symptoms on the early diagnosis of Parkinson’s disease

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Abstract

The detection of Parkinson’s disease (PD) at stages earlier than current diagnostic criteria allow for may increase the efficacy of disease-modifying therapies. Here we studied the relationship between retrospectively reported prodromal non-motor and motor features of PD, their pre-diagnostic presentation to physicians, and the extrapolated potential of an earlier diagnosis of PD considering early diagnostic markers detected at presence. One hundred and fifteen PD patients (41 women; age 63.2 ± 8.6 years) underwent a structured face-to-face interview on 22 prediagnostic symptoms. Present olfactory function, motor symptoms, and substantia nigra hyperechogenicity (SN-h) were assessed using standardized tools. Most frequently self-perceived symptoms in the early and very early prediagnostic phase (>2, >7 years prior to diagnosis) were hyposmia (23, 10 %), musculoskeletal pain (21, 9 %), and depression/anxiety (14, 11 %). In the late prediagnostic phase (≤2 years) mild motor signs, especially asymmetric bradykinesia and rest tremor, increasingly dominated the self-perception. In the prediagnostic phase, 99 % of patients consulted a physician because of motor symptoms but only 36 % with non-motor symptoms, mostly pain (20 %), depression/anxiety (9 %), constipation, bladder urgency, insomnia, REM sleep behaviour disorder, sexual dysfunction, and malignant melanoma (each, <6 %). Assuming the potential detectability of present hyposmia, asymmetric motor slowing and SN-h, a triad highly specific for PD, as early as 5 years prior to diagnosis, up to 84 (73 %) patients could have been identified in the prediagnostic phase using their or their physicians’ awareness of early symptoms. We conclude that educating the general population and physicians on the importance of distinct prodromal features and applying symptom-specific diagnostic programs can improve the early detection of PD.

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References

  1. Fearnley JM, Lees AJ (1991) Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain 114:2283–2301

    Article  PubMed  Google Scholar 

  2. Hawkes CH (2008) The prodromal phase of sporadic Parkinson’s disease: does it exist and if so how long is it? Mov Disord 23:1799–1807

    Article  PubMed  Google Scholar 

  3. Tolosa E, Gaig C, Santamaría J, Compta Y (2009) Diagnosis and the premotor phase of Parkinson disease. Neurology 72(suppl 7):S12–S20

    Article  PubMed  Google Scholar 

  4. Vingerhoets FJ, Snow BJ, Lee CS, Schulzer M, Mak E, Calne DB (1994) Longitudinal fluorodopa positron emission tomographic studies of the evolution of idiopathic parkinsonism. Ann Neurol 36:759–764

    Article  PubMed  CAS  Google Scholar 

  5. Marek K, Jennings D (2009) Can we image premotor Parkinson disease? Neurology 72(suppl 7):S21–S26

    Article  PubMed  Google Scholar 

  6. Gaenslen A, Swid I, Liepelt-Scarfone I, Godau J, Berg D (2011) The patients’ perception of prodromal symptoms before the initial diagnosis of Parkinson’s disease. Mov Disord 26:653–658

    Article  PubMed  Google Scholar 

  7. Lang AE (2011) A critical appraisal of the premotor symptoms of Parkinson’s disease: potential usefulness in early diagnosis and design of neuroprotective trials. Mov Disord 26:775–783

    Article  PubMed  Google Scholar 

  8. Stern MB, Siderowf A (2010) Parkinson’s at risk syndrome: can Parkinson’s disease be predicted? Mov Disord 25(suppl 1):S89–S93

    Article  PubMed  Google Scholar 

  9. Postuma RB, Gagnon JF, Vendette M, Desjardins C, Montplaisir JY (2011) Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder. Ann Neurol 69:811–818

    Article  PubMed  Google Scholar 

  10. Gonera EG, van’t Hof M, Berger HJ, van Weel C, Horstink MW (1997) Symptoms and duration of the prodromal phase in Parkinson’s disease. Mov Disord 12:871–876

    Article  PubMed  CAS  Google Scholar 

  11. Olsen JH, Friis S, Frederiksen K (2006) Malignant melanoma and other types of cancer preceding Parkinson disease. Epidemiology 17:582–587

    Article  PubMed  Google Scholar 

  12. Berg D, Godau J, Walter U (2008) Transcranial sonography in movement disorders. Lancet Neurol 7:1044–1055

    Article  PubMed  Google Scholar 

  13. Berg D, Behnke S, Seppi K et al (2013) Enlarged hyperechogenic substantia nigra as a risk marker for Parkinson’s disease. Mov Disord 28:216–219

    Article  PubMed  CAS  Google Scholar 

  14. Busse K, Heilmann R, Kleinschmidt S et al (2012) Value of combined midbrain sonography, olfactory and motor function assessment in the differential diagnosis of early Parkinson’s disease. J Neurol Neurosurg Psychiatry 83:441–447

    Article  PubMed  Google Scholar 

  15. Iranzo A, Lomeña F, Stockner H et al (2010) Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study. Lancet Neurol 9:1070–1077

    Article  PubMed  CAS  Google Scholar 

  16. Siderowf A, Jennings D, Eberly S et al (2012) Impaired olfaction and other prodromal features in the Parkinson At-Risk Syndrome Study. Mov Disord 27:406–412

    Article  PubMed  Google Scholar 

  17. Postuma RB, Lang AE, Gagnon JF, Pelletier A, Montplaisir JY (2012) How does parkinsonism start? Prodromal parkinsonism motor changes in idiopathic REM sleep behaviour disorder. Brain 135:1860–1870

    Article  PubMed  CAS  Google Scholar 

  18. Winkler J, Ehret R, Büttner T et al (2011) Parkinson’s disease risk score: moving to a premotor diagnosis. J Neurol 258(suppl 2):S311–S315

    Article  PubMed  Google Scholar 

  19. Berg D, Marek K, Ross GW, Poewe W (2012) Defining at-risk populations for Parkinson’s disease: lessons from ongoing studies. Mov Disord 27:656–665

    Article  PubMed  Google Scholar 

  20. Meara J, Bhowmick BK, Hobson P (1999) Accuracy of diagnosis in patients with presumed Parkinson’s disease. Age Ageing 28:99–102

    Article  PubMed  CAS  Google Scholar 

  21. Fahn S, Elton RL, Members of the UPDRS Development Committee (1987) Unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Goldstein M, Calne DB (eds) Recent developments in Parkinson’s disease II, 1st edn. Macmillan, New York, pp 153–163

    Google Scholar 

  22. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC (2006) Functional bowel disorders. Gastroenterology 130:1480–1491

    Article  PubMed  Google Scholar 

  23. Nègre-Pagès L, Regragui W, Bouhassira D, Grandjean H, Rascol O, DoPaMiP Study Group (2008) Chronic pain in Parkinson’s disease: the cross-sectional French DoPaMiP survey. Mov Disord 23:1361–1369

    Article  PubMed  Google Scholar 

  24. Chaudhuri KR, Martinez-Martin P, Schapira AH et al (2006) International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson’s disease: the NMSQuest study. Mov Disord 21:916–923

    Article  PubMed  Google Scholar 

  25. Schrag A, Barone P, Brown RG et al (2007) Depression rating scales in Parkinson’s disease: critique and recommendations. Mov Disord 22:1077–1092

    Article  PubMed  Google Scholar 

  26. Lubeck DP, Prebil LA, Peeples P, Brown JS (1999) A health related quality of life measure for use in patients with urge urinary incontinence: a validation study. Qual Life Res 8:337–344

    Article  PubMed  CAS  Google Scholar 

  27. Hummel T, Konnerth CG, Rosenheim K, Kobal G (2001) Screening of olfactory function with a four-minute odor identification test: reliability, normative data, and investigations in patients with olfactory loss. Ann Otol Rhinol Laryngol 110:976–981

    PubMed  CAS  Google Scholar 

  28. Walter U (2013) How to measure substantia nigra hyperechogenicity in Parkinson disease: detailed guide with video. J Ultrasound Med 32:1837–1843

    Article  PubMed  Google Scholar 

  29. Flohil SC, de Vries E, Neumann HA, Coebergh JW, Nijsten T (2011) Incidence, prevalence and future trends of primary basal cell carcinoma in the Netherlands. Acta Derm Venereol 91:24–30

    PubMed  Google Scholar 

  30. Husmann G, Kaatsch P, Katalinic A, Bertz J, Haberland J, Kraywinkel K, Wolf U (2010) Malignant melanoma of the skin. In: Robert Koch Institute and Association of Population-based Cancer Registries in Germany (ed) Cancer in Germany 2005/2006. Incidence and trends. Robert Koch-Institut, Berlin, pp 52–55

    Google Scholar 

  31. Haehner A, Hummel T, Hummel C, Sommer U, Junghanns S, Reichmann H (2007) Olfactory loss may be a first sign of idiopathic Parkinson’s disease. Mov Disord 22:839–842

    Article  PubMed  Google Scholar 

  32. Ross GW, Petrovitch H, Abbott RD et al (2008) Association of olfactory dysfunction with risk for future Parkinson’s disease. Ann Neurol 63:167–173

    Article  PubMed  Google Scholar 

  33. Iwanami M, Miyamoto T, Miyamoto M, Hirata K, Takada E (2010) Relevance of substantia nigra hyperechogenicity and reduced odor identification in idiopathic REM sleep behavior disorder. Sleep Med 11:361–365

    Article  PubMed  Google Scholar 

  34. Müller B, Larsen JP, Wentzel-Larsen T, Skeie GO, Tysnes OB, Parkwest Study Group (2011) Autonomic and sensory symptoms and signs in incident, untreated Parkinson’s disease: frequent but mild. Mov Disord 26:65–72

    Article  PubMed  Google Scholar 

  35. de Lau LM, Koudstaal PJ, Hofman A, Breteler MM (2006) Subjective complaints precede Parkinson disease: the Rotterdam study. Arch Neurol 63:362–365

    Article  PubMed  Google Scholar 

  36. Liu R, Gao X, Lu Y, Chen H (2011) Meta-analysis of the relationship between Parkinson disease and melanoma. Neurology 76:2002–2009

    Article  PubMed  Google Scholar 

  37. Stamey W, Davidson A, Jankovic J (2008) Shoulder pain: a presenting symptom of Parkinson disease. J Clin Rheumatol 14:253–254

    Article  PubMed  Google Scholar 

  38. Farnikova K, Krobot A, Kanovsky P (2012) Musculoskeletal problems as an initial manifestation of Parkinson’s disease: a retrospective study. J Neurol Sci 319:102–104

    Article  PubMed  Google Scholar 

  39. Leentjens AF, Van den Akker M, Metsemakers JF, Lousberg R, Verhey FR (2003) Higher incidence of depression preceding the onset of Parkinson’s disease: a register study. Mov Disord 18:414–418

    Article  PubMed  Google Scholar 

  40. Politis M, Wu K, Molloy S, Bain PG, Chaudhuri KR, Piccini P (2010) Parkinson’s disease symptoms: the patient’s perspective. Mov Disord 25:1646–1651

    Article  PubMed  Google Scholar 

  41. Paisán-Ruiz C, Houlden H (2010) Common pathogenic pathways in melanoma and Parkinson disease. Neurology 75:1653–1655

    Article  PubMed  Google Scholar 

  42. Diederich NJ, Pieri V, Hipp G, Rufra O, Blyth S, Vaillant M (2010) Discriminative power of different nonmotor signs in early Parkinson’s disease. A case-control study. Mov Disord 25:882–887

    Google Scholar 

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Acknowledgments

The authors wish to thank Mrs. Kerstin Lange und Mrs. Cornelia Berger, technical assistants at the Parkinson Clinic “Waldklinik Bernburg GmbH”, for performing the SS-12 tests.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Correspondence to Uwe Walter.

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S. Kleinschmidt and K. Busse contributed equally.

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Walter, U., Kleinschmidt, S., Rimmele, F. et al. Potential impact of self-perceived prodromal symptoms on the early diagnosis of Parkinson’s disease. J Neurol 260, 3077–3085 (2013). https://doi.org/10.1007/s00415-013-7125-6

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  • DOI: https://doi.org/10.1007/s00415-013-7125-6

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