Increased muscle activity during rapid eye movement sleep correlates with decrease of striatal presynaptic dopamine transporters. IPT and IBZM SPECT imaging in subclinical and clinically manifest idiopathic REM sleep behavior disorder, Parkinson's disease, and controls.
OBJECTIVE
Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by complex behavior during REM sleep. The etiology of this disorder is still unknown, but a recent study showed that RBD precedes symptoms of Parkinson disease (PD) by several years, and in a previous study, we found reduced striatal dopamine transporters in idiopathic clinically manifest RBD.


METHODS
Hypothesizing that subclinical RBD shows a less severe reduction of striatal dopamine transporters than clinically manifest RBD, we studied striatal postsynaptic dopamine D2-receptors with (S)-2hydroxy-3iodo-6-methoxy-([1-ethyl-2-pyrrolidinyl]methyl) benzamide labeled with iodine 123 (IBZM) and the striatal presynaptic dopamine transporters with (N)-(3-iodopropene-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane labeled with iodine 123 (IPT) using single-photon emission computed tomography (SPECT) in the following groups: 8 patients with idiopathic subclinical RBD, 8 patients with idiopathic clinically manifest RBD, 11 controls, and 8 patients with PD stage Hoehn & Yahr I.


RESULTS
The IPT uptake was highest in controls. There was a significant decrease in IPT uptake from controls to patients with subclinical RBD, from patients with subclinical RBD to clinically manifest RBD, and from patients with clinically manifest RBD to patients with PD (controls: right = 4.07 +/- 0.29, left = 4.07 +/- 0.30; subclinical RBD: right = 3.56 +/- 0.21, left = 3.55 +/- 0.25; clinically manifest RBD: right = 3.18 +/- 0.43, left = 3.2 +/- 0.43; PD: ipsilateral to the clinically affected body side = 3.25 +/- 0.35, contralateral to the clinically affected body side = 2.51 +/- 0.28). Muscle activity during REM sleep lasting persistently longer than 0.5 seconds was independently associated with reduction of striatal dopamine transporters (P = 0.001). The IBZM uptake was not significantly different between the groups.


CONCLUSIONS
This study suggests that there is a continuum of reduced striatal dopamine transporters involved in the pathophysiologic mechanisms causing increased muscle activity during REM sleep in patients with subclinical RBD.
Eisensehr
Ilonka
I
Department of Neurology, University of Munich, Germany. eisen@nefo.med.uni-muenchen.de
Linke
Reiner
R
Tatsch
Klaus
K
Kharraz
Bita
B
Gildehaus
Josef F
JF
Wetter
Christian T
CT
Trenkwalder
Claudia
C
Schwarz
Johannes
J
Noachtar
Soheyl
S
D000328:Adult; D000368:Aged; D001049:Apnea / Q000175:diagnosis / Q000453:epidemiology; D001549:Benzamides / Q000493:pharmacokinetics; D002421:Caudate Nucleus / Q000378:metabolism; D003287:Contrast Media; D003342:Corpus Striatum / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D004576:Electromyography; D005133:Eye Movements / Q000502:physiology; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000172:deficiency* / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D009801:Oculomotor Muscles / Q000294:innervation / Q000502:physiology*; D017286:Polysomnography; D011446:Prospective Studies; D011699:Putamen / Q000378:metabolism; D011759:Pyrrolidines / Q000493:pharmacokinetics; D020187:REM Sleep Behavior Disorder / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D017661:Receptors, Presynaptic / Q000378:metabolism*; D012891:Sleep Apnea Syndromes / Q000175:diagnosis / Q000453:epidemiology; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon
D001549:Benzamides; D003287:Contrast Media; D065127:Dopamine D2 Receptor Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011759:Pyrrolidines; D017661:Receptors, Presynaptic; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide