Dopamine transporter imaging with [123I]-beta-CIT demonstrates presynaptic nigrostriatal dopaminergic damage in Wilson's disease.
OBJECTIVE
The most common neurological manifestations in Wilson's disease are parkinsonism and dystonia. These are assumed to be due to striatal injury, which has been repeatedly demonstrated by pathology and CT or MRI. The substantia nigra has not been shown to be damaged in pathological studies. However, there have been clinical and imaging studies suggesting presynaptic nigrostriatal injury. (1r)-2Beta-carbomethoxy-3beta-(4-iodophenyl)tropane (beta-CIT) is a specific ligand that binds to the dopamine transporter (DAT), and can examine the integrity of dopaminergic nerve terminals. Evidence for presynaptic nigrostriatal dopaminergic damage in Wilson's disease was searched for using [123I]-beta-CIT SPECT.


METHODS
Six patients with Wilson's disease were studied, together with 15 healthy normal controls, and six patients with Parkinson's disease. After injection of [123I]-beta-CIT, SPECT studies were done at 18 hours. Specific striatal/occipital binding ratio (S/O ratio) was calculated as (striatal binding-occipital binding)/occipital binding.


RESULTS
The specific S/O ratios were 6.22 (1.32) (mean (SD)) in normal volunteers, 3.78 (0.65) in Parkinson's disease, and 3.60 (0.49) in Wilson's disease.


CONCLUSIONS
There was severe loss of the DAT in the striatum suggesting significant damage in presynaptic nigrostriatal dopaminergic nerve terminals. Therefore, a presynaptic lesion may contribute to neurological manifestations in Wilson's disease.
Department of Neurology and Nuclear Medicine, College of Medicine, Seoul National University, Seoul National University Hospital, Korea. jeonmd@plaza.snu.ac.kr
B
B
Jeon
J M
JM
Kim
J M
JM
Jeong
K M
KM
Kim
Y S
YS
Chang
D S
DS
Lee
M C
MC
Lee
D000293:Adolescent; D000328:Adult; D001931:Brain Mapping; D002352:Carrier Proteins / Q000502:physiology*; D003042:Cocaine / Q000031:analogs & derivatives; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology; D050483:Dopamine Plasma Membrane Transport Proteins; D004421:Dystonia / Q000000981:diagnostic imaging* / Q000503:physiopathology; D005260:Female; D006527:Hepatolenticular Degeneration / Q000000981:diagnostic imaging* / Q000503:physiopathology; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D009460:Neurologic Examination; D009778:Occipital Lobe / Q000000981:diagnostic imaging / Q000503:physiopathology; D010302:Parkinson Disease, Secondary / Q000000981:diagnostic imaging* / Q000503:physiopathology; D013378:Substantia Nigra / Q000000981:diagnostic imaging* / Q000503:physiopathology; D015899:Tomography, Emission-Computed, Single-Photon
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine; D004298:Dopamine