Obstructive sleep apnea is related to a thalamic cholinergic deficit in MSA.
OBJECTIVE
To explore the neurochemical basis of obstructive sleep apnea (OSA) in multiple-system atrophy (MSA).


METHODS
In 13 patients with probable MSA, nocturnal, laboratory-based polysomnography was used to rate the severity of OSA using the apnea-hypopnea index during sleep. SPECT with (-)-5-[123I]iodobenzovesamicol ([123I]IBVM) was utilized to measure the density of thalamic cholinergic terminals, which project from the brainstem pedunculopontine and laterodorsal tegmental nuclei. PET with (+)-[11C]dihydrotetrabenazine ([11C]DTBZ) was also used to measure the density of striatal monoaminergic terminals, which project from the brainstem. Findings in the patient group were compared with data from 12 normal control subjects scanned utilizing [123I]IBVM and 15 normal control subjects utilizing [11C]DTBZ.


RESULTS
Age and gender distributions were similar in patient and control groups. The MSA subjects showed decreased [123I]IBVM binding in the thalamus (p < 0.001) and decreased mean [11C]DTBZ binding in the striatum (p < 0.0001) in comparison with the control subjects. In the MSA group, thalamic [123I]IBVM binding was inversely correlated with the severity of OSA (p = 0.011). Striatal [11C]DTBZ binding was not correlated with the severity of OSA (p = 0.19).


CONCLUSIONS
Decreased pontine cholinergic projections may contribute to OSA in MSA.
Gilman
S
S
Department of Neurology University of Michigan, Ann Arbor, USA. sgilman@umich.edu
Chervin
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RD
Koeppe
R A
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Consens
F B
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Little
R
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An
H
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Junck
L
L
Heumann
M
M
D000328:Adult; D017677:Age Distribution; D000368:Aged; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D009479:Neuropeptides; D010865:Pilot Projects; D010880:Piperidines; D011149:Pons / Q000503:physiopathology; D011950:Receptors, Cholinergic / Q000172:deficiency* / Q000378:metabolism; D012016:Reference Values; D012044:Regression Analysis; D017678:Sex Distribution; D020181:Sleep Apnea, Obstructive / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism*; D013747:Tetrabenazine / Q000031:analogs & derivatives*; D013764:Tetrahydronaphthalenes; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism*; D014055:Tomography, Emission-Computed; D015899:Tomography, Emission-Computed, Single-Photon; D050494:Vesicular Acetylcholine Transport Proteins; D050492:Vesicular Biogenic Amine Transport Proteins; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D010880:Piperidines; D011950:Receptors, Cholinergic; C493459:SLC18A3 protein, human; D013764:Tetrahydronaphthalenes; D050494:Vesicular Acetylcholine Transport Proteins; D050492:Vesicular Biogenic Amine Transport Proteins; D033921:Vesicular Transport Proteins; C065043:5-iodobenzovesamicol; C032811:dihydrotetrabenazine; D013747:Tetrabenazine