Skip to main content
SpringerLink
Log in

Das präsymptomatische Stadium neurodegenerativer Erkrankungen

The presymptomatic stage of neurodegenerative disorders

  • Leitthema
  • Published:
Der Nervenarzt Aims and scope Submit manuscript

Zusammenfassung

Neurodegenerative Erkrankungen wie Chorea Huntington, spinozerebelläre Ataxien, M. Parkinson oder M. Alzheimer manifestieren sich im Erwachsenenalter mit langsam progredienten, aber unaufhaltsamen Symptomen. In diesem Stadium suchen die meisten Patienten einen Arzt auf, der eine eindeutige Diagnose stellen kann. Es ist jedoch gut belegt, dass der sichtbaren Erkrankung ein präsymptomatisches Krankheitsstadium vorausgeht, das mehrere Jahre dauern kann. Ein eindrucksvolles Beispiel ist der M. Parkinson, bei dem bereits mehr als die Hälfte der dopaminergen Neuronen der Substantia nigra verloren ist, bevor sich erste motorische Zeichen entwickeln. Untersuchungen des präsymptomatischen Stadiums neurodegenerativer Erkrankungen sind für ein verbessertes Verständnis dieser Erkrankungen und die Entwicklung präventiver Strategien von zentraler Bedeutung. Es ist daher wichtig, die frühesten und sensitivsten klinischen Zeichen und biologischen Marker zu identifizieren, die den Beginn der Erkrankung ankündigen. Weiterhin können durch das Studium präsymptomatischer Krankheitsstadien kompensatorische Mechanismen aufgedeckt werden, die eine scheinbar normale Hirnfunktion bei fortschreitender Neurodegeneration gewährleisten.

Summary

Neurodegenerative disorders, such as Huntington’s disease, spinocerebellar ataxias, Parkinson’s disease or Alzheimer’s disease, manifest in adult age with insidiously developing, slowly progressing symptoms. At this stage, most patients consult a doctor, and a definite diagnosis can be made. It is, however, well established that the manifest disease is preceded by a presymptomatic disease stage that may last for years. A striking example is Parkinson’s disease, in which more than half of the dopaminergic neurons of the substantia nigra are lost before motor symptoms appear. Studies of the presymptomatic stage of neurodegenerative disorders are pivotal for an advanced understanding of these disorders and the development of preventive strategies aimed at postponing the clinical onset of these disorders. It is therefore important to identify the earliest and most sensitive clinical signs and biological markers that herald the onset of the illness. Furthermore, studies of presymptomatic disease stages are important because they may help to unravel compensatory mechanisms responsible for apparently normal brain function despite ongoing neurodegeneration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2

Literatur

  1. Halliday GM, Fedorow H, Rickert CH et al (2006) Evidence for specific phases in the development of human neuromelanin. J Neural Transm 113(6):721–728

    Article  PubMed  CAS  Google Scholar 

  2. Klein C, Krainc D, Schlossmacher MG, Lang AE (2011) Translational research in neurology and neuroscience 2011: movement disorders. Arch Neurol (in press)

  3. Paulson HL, Fischbeck KH (1996) Trinucleotide repeats in neurogenetic disorders. Annu Rev Neurosci 19:79–107

    Article  PubMed  CAS  Google Scholar 

  4. Bruggemann N, Vegt J, Klein C, Siebner HR (2010) Imaging of genetic aspects of Parkinson’s disease. Nervenarzt 81(10):1196–1203

    Article  PubMed  CAS  Google Scholar 

  5. Nuenen BF van, Weiss MM, Bloem BR et al (2009) Heterozygous carriers of a Parkin or PINK1 mutation share a common functional endophenotype. Neurology 72(12):1041–1047

    Article  PubMed  Google Scholar 

  6. Vaccarino AL, Anderson K, Borowsky B et al (2011) An item response analysis of the motor and behavioral subscales of the unified Huntington’s disease rating scale in Huntington disease gene expansion carriers. Mov Disord 26(5):877–884

    Article  PubMed  Google Scholar 

  7. Paulsen JS, Langbehn DR, Stout JC et al (2008) Detection of Huntington’s disease decades before diagnosis: the Predict-HD study. J Neurol Neurosurg Psychiatry 79(8):874–880

    Article  PubMed  CAS  Google Scholar 

  8. Tabrizi SJ, Langbehn DR, Leavitt BR et al (2009) Biological and clinical manifestations of Huntington’s disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data. Lancet Neurol 8(9):791–801

    Article  PubMed  Google Scholar 

  9. Tabrizi SJ, Scahill RI, Durr A et al (2011) Biological and clinical changes in premanifest and early stage Huntington’s disease in the TRACK-HD study: the 12-month longitudinal analysis. Lancet Neurol 10(1):31–42

    Article  PubMed  Google Scholar 

  10. Sturrock A, Laule C, Decolongon J et al (2010) Magnetic resonance spectroscopy biomarkers in premanifest and early Huntington disease. Neurology 75(19):1702–1710

    Article  PubMed  CAS  Google Scholar 

  11. Durr A (2010) Autosomal dominant cerebellar ataxias: polyglutamine expansions and beyond. Lancet Neurol 9(9):885–894

    Article  PubMed  CAS  Google Scholar 

  12. Schmitz-Hubsch T, Coudert M, Bauer P et al (2008) Spinocerebellar ataxia types 1, 2, 3, and 6: disease severity and nonataxia symptoms. Neurology 71(13):982–989

    Article  PubMed  CAS  Google Scholar 

  13. Jacobi H, Bauer P, Giunti P et al (2011) The naturalhistory of spinocerebellar ataxia type1, 2, 3, and 6: a 2-year follow-up study. Neurology (in press)

  14. Globas C, Montcel ST du, Baliko L et al (2008) Early symptoms in spinocerebellar ataxia type 1, 2, 3, and 6. Mov Disord 23(15):2232–2238

    Article  PubMed  Google Scholar 

  15. Velazquez-Perez L, Diaz R, Perez-Gonzalez R et al (2009) Motor decline in clinically presymptomatic spinocerebellar ataxia type 2 gene carriers. PLoS One 4(4):e5398

    Article  PubMed  Google Scholar 

  16. Rodriguez-Labrada R, Velazquez-Perez L, Ochoa NC et al (2011) Subtle rapid eye movement sleep abnormalities in presymptomatic spinocerebellar ataxia type 2 gene carriers. Mov Disord 26(2):347–350

    Article  PubMed  Google Scholar 

  17. Christova P, Anderson JH, Gomez CM (2008) Impaired eye movements in presymptomatic spinocerebellar ataxia type 6. Arch Neurol 65(4):530–536

    Article  PubMed  Google Scholar 

  18. Nalls MA, Plagnol V, Hernandez DG et al (2011) Imputation of sequence variants for identification of genetic risks for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet 377(9766):641–649

    Article  PubMed  Google Scholar 

  19. Eggers C, Schmidt A, Hagenah J et al (2010) Progression of subtle motor signs in PINK1 mutation carriers with mild dopaminergic deficit. Neurology 74(22):1798–1805

    Article  PubMed  CAS  Google Scholar 

  20. Baba T, Takeda A, Kikuchi A et al (2011) Association of olfactory dysfunction and brain. Metabolism in Parkinson’s disease. Mov Disord 26(4):621–628

    Article  PubMed  Google Scholar 

  21. Fujishiro H, Frigerio R, Burnett M et al (2008) Cardiac sympathetic denervation correlates with clinical and pathologic stages of Parkinson’s disease. Mov Disord 23(8):1085–1092

    Article  PubMed  Google Scholar 

  22. Postuma RB, Gagnon JF, Montplaisir J (2011) Clinical prediction of Parkinson’s disease: planning for the age of neuroprotection. J Neurol Neurosurg Psychiatry 81(9):1008–1013

    Article  Google Scholar 

  23. Berg D (2011) Substantia nigra hyperechogenicity is a risk marker of Parkinson’s disease: yes. J Neural Transm 118(4):613–619

    Article  PubMed  Google Scholar 

  24. Hagenah JM, Becker B, Bruggemann N et al (2008) Transcranial sonography findings in a large family with homozygous and heterozygous PINK1 mutations. J Neurol Neurosurg Psychiatry 79(9):1071–1074

    Article  PubMed  CAS  Google Scholar 

  25. Della Sala S, Cocchini G, Logie RH et al (2010) Dual task during encoding, maintenance, and retrieval in Alzheimer’s disease. J Alzheimers Dis 19(2):503–515

    Google Scholar 

  26. Braak E, Griffing K, Arai K et al (1999) Neuropathology of Alzheimer’s disease: what is new since A. Alzheimer? Eur Arch Psychiatry Clin Neurosci 249(Suppl 3):14–22

    PubMed  Google Scholar 

  27. Wang PN, Lirng JF, Lin KN et al (2006) Prediction of Alzheimer’s disease in mild cognitive impairment: a prospective study in Taiwan. Neurobiol Aging 27(12):1797–1806

    Article  PubMed  CAS  Google Scholar 

  28. Lerch JP, Pruessner J, Zijdenbos AP et al (2008) Automated cortical thickness measurements from MRI can accurately separate Alzheimer’s patients from normal elderly controls. Neurobiol Aging 29(1):23–30

    Article  PubMed  Google Scholar 

  29. Zhou J, Greicius MD, Gennatas ED et al (2010) Divergent network connectivity changes in behavioural variant frontotemporal dementia and Alzheimer’s disease. Brain 133(5):1352–1367

    Article  PubMed  Google Scholar 

  30. Blennow K, Hampel H (2003) CSF markers for incipient Alzheimer’s disease. Lancet Neurol 2(10):605–613

    Article  PubMed  CAS  Google Scholar 

  31. Hansson O, Zetterberg H, Buchhave P et al (2006) Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol 5(3):228–234

    Article  PubMed  CAS  Google Scholar 

Download references

Danksagung

Christine Klein wird durch Fördergelder von der Hermann und Lilly Schilling-Stiftung, der Volkswagenstiftung, der DFG, des BMBF, der EU und der Universität zu Lübeck unterstützt.

Thomas Klockgether wird durch Fördergelder der DFG, des BMBF und der Else Kröner-Fresenius-Stiftung unterstützt.

Thomas Münte wird durch die DFG und das BMBF unterstützt.

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. Sektion für Klinische und Molekulare Neurogenetik, Klinik für Neurologie, Universität zu Lübeck, Lübeck, Deutschland

    C. Klein & J. Hagenah

  2. Klinik für Neurologie, Universität zu Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Deutschland

    C. Klein, J. Hagenah & T. Münte

  3. Klinik für Neurologie, Universitätsklinikum Ulm, Ulm, Deutschland

    B. Landwehrmeyer

  4. Klinik für Neurologie, Universitätsklinikum Bonn, Bonn, Deutschland

    T. Klockgether

  5. Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Bonn, Bonn, Deutschland

    T. Klockgether

Authors
  1. C. Klein
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Hagenah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Landwehrmeyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T. Münte
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T. Klockgether
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Klein.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Klein, C., Hagenah, J., Landwehrmeyer, B. et al. Das präsymptomatische Stadium neurodegenerativer Erkrankungen. Nervenarzt 82, 994–1001 (2011). https://doi.org/10.1007/s00115-011-3258-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00115-011-3258-y

Schlüsselwörter

Keywords

Search

Navigation