Clinical markers of early nigrostriatal neurodegeneration in idiopathic rapid eye movement sleep behavior disorder.
BACKGROUND
Rapid eye movement sleep behavior disorder (RBD) is an early feature in α synucleinopathies and may precede other clinical manifestations of disease for several years. Olfactory dysfunction and mild motor abnormalities (MMAs) are highly prevalent in prodromal α synucleinopathies such as RBD and are suspected to be predictive neurodegenerative markers. Because both markers also are highly prevalent in the healthy elderly population, the discriminative value to detect an early neurodegenerative process is unclear.


METHODS
We examined 28 patients with idiopathic RBD (iRBD) without manifest neurodegenerative disease to determine diagnostic accuracy of MMAs and olfactory dysfunction in identifying patients with early nigrostriatal degeneration in transcranial sonography (TCS) and (123)I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single-photon emission computed tomography ((123)I-FP-CIT-SPECT).


RESULTS
Sixty-three percent of our participants showed MMAs which were strongly associated with abnormal TCS and (123)I-FP-CIT-SPECT findings. The discriminative value in detecting participants with early nigrostriatal degeneration was excellent (area under the receiver operating characteristic [ROC] curve, 0.84 [P≤.003] for TCS and 0.79 [P≤.066] for (123)I-FP-CIT-SPECT). Olfactory dysfunction was present in 78% of iRBD participants, but it was not linked with neuroimaging abnormalities or MMAs. Olfactory dysfunction did not discriminate participants with early nigrostriatal degeneration (area under the ROC curve, 0.54 [P≤.747] for TCS and 0.31 [P≤.225] for (123)I-FP-CIT-SPECT). Early RBD manifestation but no demographic (e.g., age, gender) or clinical characteristics of RBD (e.g., duration, severity of RBD) were associated with neuroimaging abnormalities in TCS and (123)I-FP-CIT-SPECT.


CONCLUSIONS
Unlike olfactory dysfunction, MMAs discriminate patients with early nigrostriatal degeneration in iRBD. Early RBD manifestation seems to be an additional risk factor which aggravates neurodegenerative risk.
Hans-Berger Department of Neurology, University Hospital Jena, Germany. Electronic address: Sven.Rupprecht@med.uni-jena.de.
Sven
S
Rupprecht
Björn
B
Walther
Hilmar
H
Gudziol
Jörg
J
Steenbeck
Martin
M
Freesmeyer
Otto W
OW
Witte
Albrecht
A
Günther
Matthias
M
Schwab
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000378:metabolism; D000857:Olfaction Disorders / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000378:metabolism; D015995:Prevalence; D020187:REM Sleep Behavior Disorder / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000378:metabolism; D012307:Risk Factors; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D017585:Ultrasonography, Doppler, Transcranial; D051844:alpha-Synuclein / Q000378:metabolism*
D051844:alpha-Synuclein
(123)I-FP-CIT SPECT; Diagnostic accuracy; Mild motor abnormalities; Olfactory dysfunction; REM sleep behavior disorder; Transcranial sonography; α-Synucleinopathy