Skip to main content
SpringerLink
Log in

Bildgebende Verfahren als Biomarker der Neurodegeneration bei der REM-Schlafverhaltensstörung

Neuroimaging methods as biomarkers of neurodegeneration in REM sleep behavior disorder

  • Übersichten
  • Published:
Somnologie - Schlafforschung und Schlafmedizin Aims and scope Submit manuscript

Zusammenfassung

Hintergrund

Die REM-Schlaf-Verhaltensstörung (RBD) ist eine Parasomnie, die durch den Verlust der im REM-Schlaf normalerweise vorliegenden Muskelatonie gekennzeichnet ist. Über 80 % der Patienten mit idiopathischer RBD entwickeln im späteren Verlauf eine α-Synukleinopathie, d. h. eine Parkinson-Krankheit, eine Demenz mit Lewy-Körpern oder in selteneren Fällen eine Multisystematrophie. Die RBD stellt somit ein hochspezifischer präklinischer Marker dieser neurodegenerativen Erkrankungen dar.

Ziel muss es sein, die prämotorische Phase dieser neurodegenerativen Parkinson-Syndrome soweit zu charakterisieren, um zukünftig die Krankheitsprogression mit krankheitsmodifizierenden Therapieansätzen beeinflussen zu können. Das erfordert gleichsam eine möglichst frühe Differenzierung der verschiedenen Verlaufsformen.

Ziel der Arbeit

Es sollen die bildgebenden Verfahren, die als Biomarker der Neurodegeneration bei der REM-Schlafverhaltensstörung dienen können, in einer Übersicht dargestellt werden.

Methode

Selektive Literaturrecherche.

Ergebnisse und Diskussion

Die Echogenität der Substantia nigra kann mittels transkranieller Hirnparenchymsonographie beurteilt werden. Patienten mit RBD zeigen in etwa 40 % der Fälle eine Hyperechogenität der Substantia nigra. Diese scheint – wie bei der Parkinson-Krankheit – nicht zur Beurteilung der Krankheitsprogression geeignet, kann aber in der Kombination mit anderen diagnostischen Verfahren als Risikomarker dienen. Die Darstellung des präsynaptischen Dopamintransporters in SPECT-Technik kann die nigrostriatale Degeneration abbilden und eignet sich zudem zur Erfassung der Krankheitsprogression. Dies würde auch das Monitoring möglicher krankheitsmodifizierender Therapien erlauben. Mit der Darstellung des Glukosestoffwechsels mit der PET scheint in der Zukunft auch eine frühzeitige Einordnung des neurodegenerativen Prozesses möglich. Mit modernen MRT-Verfahren können strukturelle Veränderungen bei Patienten mit RBD bislang nur auf Gruppenniveau nachgewiesen werden.

Abstract

Background

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by a loss of muscle atonia during REM sleep. More than 80 % of patients initially diagnosed with idiopathic RBD eventually develop synucleinopathies, such as Parkinson’s disease (PD), dementia with Lewy bodies and multiple system atrophy; therefore, RBD is considered to be a highly specific preclinical marker of these neurodegenerative diseases. Different imaging techniques aim to characterize RBD patients over time to better understand the natural history of the neurodegenerative process. They might have the potential to serve as non-invasive biomarkers for early and differential diagnosis and, in addition, offer the possibility to monitor the effect of disease-modifying therapies in the future.

Objective

This article presents a review of the imaging methods which can serve as biomarkers of neurodegeneration in RBD.

Methods

A selective literature search was carried out for publications relevant for this topic.

Results and discussion

Transcranial sonography allows an evaluation of the echogenicity of the substantia nigra. In patients with RBD a hyperechogenicity of the substantia nigra is found in approximately 40 % of the cases; however, as in PD, hyperechogenicity of the substantia nigra can serve as a stable risk marker in combination with other diagnostic measures rather than a tool for monitoring disease progression.

Presynaptic dopamine transporter imaging with single photon emission computed tomography (SPECT) can detect nigrostriatal degeneration in patients with RBD and monitor disease progression. Therefore, this would also allow monitoring of potential disease-modifying therapies. The visualization of glucose metabolism with positron emission tomography (PET) might be an option to prematurely differentiate the neurodegenerative process in the future. Using modern magnetic resonance imaging (MRI) methods structural alterations in patients with RBD can be demonstrated; however, so far only at a group level.

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

Literatur

  1. Becker G, Seufert J, Bogdahn U et al (1995) Degeneration of substantia nigra in chronic Parkinson’s disease visualized by transcranial color-coded real-time sonography. Neurology 45(1):182–184

    Article  CAS  PubMed  Google Scholar 

  2. Behnke S, Berg D, Naumann M et al (2005) Differentiation of Parkinson’s disease and atypical parkinsionan syndromes by transcranial sound. J Neurol Neurosurg Psychiatry 76:423–425

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Behnke S, Runkel A, Kassar HA et al (2013) Long-term course of substantia nigra hyperechogenicity in Parkinson’s disease. Mov Disord 28(4):455–459

    Article  PubMed  Google Scholar 

  4. Benamer TS, Patterson J, Grosset DG et al (2000) Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group. Mov Disord 15(3):503–510

    Article  CAS  PubMed  Google Scholar 

  5. Berg D, Becker G, Zeiler B et al (1999) Vulnerability of the nigrostriatal system as detected by transcranial ultrasound. Neurology 53(5):1026–1031

    Article  CAS  PubMed  Google Scholar 

  6. Boeve BF, Silber MH, Saper CB et al (2007) Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain 130(11):2770–2788

    Article  CAS  PubMed  Google Scholar 

  7. Braak H, Del Tredici K, Rub U et al (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211

    Article  PubMed  Google Scholar 

  8. Eisensehr I, Linke R, Noachtar S et al (2000) Reduced striatal dopamine transporters in idiopathic rapid eye movement sleep behaviour disorder. Comparison with Parkinson’s disease and controls. Brain 123(6):1155–1160

    Article  PubMed  Google Scholar 

  9. Ellmore TM, Hood AJ, Castriotta RJ et al (2010) Reduced volume of the putamen in REM sleep behavior disorder patients. Parkinsonism Relat Disord 16:645–649

    Article  PubMed  Google Scholar 

  10. Fujishiro H, Iseki E, Murayama N et al (2010) Diffuse occipital hypometabolism on [18 F]-FDG PET scans in patients with idiopathic REM sleep behavior disorder: prodromal dementia with Lewy bodies? Psychogeriatrics 10(3):144–152

    Article  PubMed  Google Scholar 

  11. Gaenslen A, Unmuth B, Godau J et al (2008) The specificity and sensitivity of transcranial ultrasound in the differential diagnosis of Parkinson’s disease: a prospective blinded study. Lancet Neurol 7:417–424

    Article  PubMed  Google Scholar 

  12. García-Lorenzo D, Longo-Dos Santos C, Ewenczyk C et al (2013) The coeruleus/subcoeruleus complex in rapid eye movement sleep behaviour disorders in Parkinson’s disease. Brain 136(7):2120–2129

    Article  PubMed Central  PubMed  Google Scholar 

  13. Holtbernd F, Gagnon JF, Postuma RB et al (2014) Abnormal metabolic network activity in REM sleep behavior disorder. Neurology 82(7):620–627

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. 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 [corrected]. Lancet Neurol 9(11):1070–1077

    Article  CAS  PubMed  Google Scholar 

  15. Iranzo A, Tolosa E, Gelpi E et al (2013) Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study. Lancet Neurol 12(5):443–453

    Article  PubMed  Google Scholar 

  16. Iranzo A, Valldeoriola F, Lomena F et al (2011) Serial dopamine transporter imaging of nigrostriatal function in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study. Lancet Neurol 10:797–805

    Article  CAS  PubMed  Google Scholar 

  17. Iwanami M, Miyamoto T, Miyamoto M et al (2010) Relevance of substantia nigra hyperechogenicity and reduced odor identification in idiopathic REM sleep behavior disorder. Sleep Med 11(4):361–365

    Article  PubMed  Google Scholar 

  18. Miyamoto M, Miyamoto T (2013) Neuroimaging of rapid eye movement sleep behavior disorder: transcranial ultrasound, single-photon emission computed tomography, and positron emission tomography scan data. Sleep Med 14(8):739–743

    Article  PubMed  Google Scholar 

  19. Miyamoto M, Miyamoto T, Iwanami M et al (2012) Preclinical substantia nigra dysfunction in rapid eye movement sleep behaviour disorder. Sleep Med 13(1):102–106

    Article  PubMed  Google Scholar 

  20. Oertel WH, Depboylu C, Krenzer M et al (2014) REM sleep behavior disorder as a prodromal stage of α-synucleinopathies: symptoms, epidemiology, pathophysiology, diagnosis and therapy. Nervenarzt 85(1):19–25

    Article  CAS  PubMed  Google Scholar 

  21. Ohtsuka C, Sasaki M, Konno K et al (2013) Changes in substantia nigra and locus coeruleus in patients with early-stage Parkinson’s disease using neuromelanin-sensitive MR imaging. Neurosci Lett 541:93–98

    Article  CAS  PubMed  Google Scholar 

  22. Schenck CH, Boeve BF, Mahowald MW (2013) Delayed emergence of a parkinsonian disorder or dementia in 81 % of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series. Sleep Med 14(8):744–748

    Article  PubMed  Google Scholar 

  23. Schenck CH, Bundlie SR, Ettinger MG et al (1986) Chronic behavioral disorders of human REM sleep: a new category of parasomnia. Sleep 9(2):293–308

    CAS  PubMed  Google Scholar 

  24. Schenck CH, Bundlie SR, Mahowald MW (1996) Delayed emergence of a parkinsonian disorder in 38 % of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology 46(2):388–393 (Erratum in: Neurology 1996;46(6):1787)

  25. Scherfler C, Frauscher B, Schocke M et al (2011) White and gray matter abnormalities in idiopathic rapid eye movement sleep behavior disorder: a diffusion-tensor imaging and voxel-based morphometry study. Ann Neurol 69(2):400–407

    Article  PubMed  Google Scholar 

  26. Spiegel J, Hellwig D, Mollers M et al (2006) Transcranial sonography and [123I]-FP-CIT SPECT disclose complementary aspects of Parkinson’s disease. Brain 129:1188–1193

    Article  PubMed  Google Scholar 

  27. Stiasny-Kolster K, Doerr Y, Möller JC et al (2005) Combination of ‚idiopathic‘ REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT. Brain 128(1):126–137

    Article  CAS  PubMed  Google Scholar 

  28. Stockner H, Iranzo A, Seppi K et al (2009) Midbrain hyperechogenicity in idiopathic REM sleep behavior disorder. Mov Disord 24(13):1906–1909

    Article  PubMed  Google Scholar 

  29. Teune LK, Bartels AL, Jong BM de et al (2010) Typical cerebral metabolic patterns in neurodegenerative brain diseases. Mov Disord 25(14):2395–2404

    Article  PubMed  Google Scholar 

  30. Unger MM, Belke M, Menzler K et al (2010) Diffusion tensor imaging in idiopathic REM sleep behavior disorder reveals microstructural changes in the brainstem, substantia nigra, olfactory region, and other brain regions. Sleep 33(6):767–773

    PubMed Central  PubMed  Google Scholar 

  31. Unger MM, Möller JC, Stiasny-Kolster K et al (2008) Assessment of idiopathic rapid-eye-movement sleep behavior disorder by transcranial sonography, olfactory function test, and FP-CIT-SPECT. Mov Disord 23(4):596–599

    Article  PubMed  Google Scholar 

  32. Vlaar AM, Bouwmans A, Mess WH et al (2009) Transcranial duplex in the differential diagnosis of parkinsonian syndromes: a systematic review. J Neurol 256:530–538

    Article  PubMed  Google Scholar 

Download references

Einhaltung ethischer Richtlinien

Interessenkonflikt. V. Ries, D. Vadasz, M. Belke, W.H. Oertel und S. Knake geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

Author information

Authors and Affiliations

  1. Klinik für Neurologie, Philipps-Universität Marburg, Baldingerstr., 35043, Marburg, Deutschland

    V. Ries, D. Vadasz, M. Belke, W.H. Oertel & S. Knake

Authors
  1. V. Ries
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Vadasz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Belke
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W.H. Oertel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Knake
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. Ries.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ries, V., Vadasz, D., Belke, M. et al. Bildgebende Verfahren als Biomarker der Neurodegeneration bei der REM-Schlafverhaltensstörung. Somnologie 18, 269–273 (2014). https://doi.org/10.1007/s11818-014-0686-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11818-014-0686-5

Schlüsselwörter

Keywords

Search

Navigation