NIGROSTRIATAL DOPAMINERGIC FUNCTION IN FAMILIAL AMYOTROPHIC-LATERAL-SCLEROSIS PATIENTS WITH AND WITHOUT COPPER ZINC SUPEROXIDE-DISMUTASE MUTATIONS/

Some cases of familial amyotrophic lateral sclerosis (FALS) are associ ated with copper/zinc superoxide dismutase (Cu/Zn-SOD) mutations, whic h are implicated in the death of motor neurons. Because Cu/ZnSOD is pr esent in high amounts in nigrostriatal dopaminergic neurons, we consid ered the possibility that FALS may be associated with subclinical nigr ostriatal dopaminergic dysfunction. We used [F-18]fluorodopa (FDOPA) a nd PET to study 14 FALS patients (50+/-11 years [mean+/-SD]): seven wi th (FALS-1) and seven without (FALS-0) Cu/Zn-SOD mutations. Fourteen a ge-matched normal volunteers (48+/-18 years) served as controls. Stria to-occipital ratios (SORs) for the caudate and the putamen were calcul ated. Five of the 14 FALS patients had reduced striatal FDOPA uptake i n the caudate nucleus, putamen, or both. Mean caudate SOR did not diff er among FALS-1, FALS-0, and control subjects. Mean putamen SOR was si gnificantly abnormal in FALS-0 but not in FALS-1 patients. These findi ngs indicate that subclinical nigrostriatal dopaminergic dysfunction i s present in some FALS patients and that FDOPA/PET abnormalities are m ore likely to be associated with FALS-0 status. This suggests that SOD mutations are less cytotoxic to dopaminergic than to motor neurons.