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.
Literatur
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
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
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
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
Berg D, Becker G, Zeiler B et al (1999) Vulnerability of the nigrostriatal system as detected by transcranial ultrasound. Neurology 53(5):1026–1031
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
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
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
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
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
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
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
Holtbernd F, Gagnon JF, Postuma RB et al (2014) Abnormal metabolic network activity in REM sleep behavior disorder. Neurology 82(7):620–627
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
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
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
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
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
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
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
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
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
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
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)
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
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
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
Stockner H, Iranzo A, Seppi K et al (2009) Midbrain hyperechogenicity in idiopathic REM sleep behavior disorder. Mov Disord 24(13):1906–1909
Teune LK, Bartels AL, Jong BM de et al (2010) Typical cerebral metabolic patterns in neurodegenerative brain diseases. Mov Disord 25(14):2395–2404
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
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
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
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
Corresponding author
Rights and permissions
About this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11818-014-0686-5