W. Douglas Brown

Age-Related Declines in Nigral Neuronal Function Correlate With Motor Impairments in Rhesus Monkeys

Although the role of dopamine dysfunction is well established in Parkinsons disease, the effect of nigrostriatal degeneration on motor performance during normal aging is less well understood. In this study, aged rhesus monkeys (25–27 years old) displayed significant impairments relative to young (3–5 years old) cohorts in motor function as assessed on a fine motor task and home cage activity. Additionally, the clinical motor function of aged monkeys was impaired relative to young monkeys as assessed on a clinical rating scale. Unbiased stereologic measurements of the substantia nigra revealed a significant age‐related loss of tyrosine hydroxylase‐immunoreactive (TH‐ir; 50.3%) and dopamine transporter‐immunoreactive (DAT‐ir; 33.2%) nigral neurons. The monkeys performance on the fine motor task and on the clinical rating scale was correlated with TH‐ir neuronal counts. The number of DAT‐ir nigral neurons was correlated with activity and clinical rating scale scores. Our results suggest that age‐related motor impairments in nonhuman primates are associated with spontaneous decreases in TH‐ir and DAT‐ir nigral cells. The correlation of motor deficits with the loss of TH‐ir and DAT‐ir nigral neurons suggests that aged nonhuman primates may provide a useful model for mimicking changes seen in human aging and early Parkinsons disease. J. Comp. Neurol. 401:253–265, 1998.

Sarcoidosis of the spinal cord with extensive vertebral involvement: A case report

We report on a patient with systemic sarcoidosis who was presented with myelopathy and backache. Plain spinal films were normal, CT scan showed sclerotic lesions within the vertebrae. MRI showed more extensive involvement of the spine with multiple vertebral lesions which were hypointense on both T1W1 and T2W1 and did not enhance with gadolinium. MRI also showed high signal lesions within the cervical and lumbar spinal cord on T2-weighted images (T2W1) which were isointense on T1-weighted images (T1W1) and did not enhance. Vertebral biopsy results were consistent with the diagnosis of sarcoidosis. MRI is very sensitive in detecting sarcoidosis of bone but non-specific and other types of sclerotic or lytic bone lesions (notably metastases) need to be excluded.

Rate of 6‐[18F]fluorodopa uptake decline in striatal subregions in Parkinson's disease

Rate of decline in 6‐L‐[18F]fluorodopa (FDOPA) uptake within the striatum has been reported as showing regional differences in Parkinsons disease (PD).

Localization of Trapping of 6-[18F] Fluoro-L-m-tyrosine, an Aromatic L-Amino Acid Decarboxylase Tracer for PET

The purpose of this study was to address four major questions regarding 6‐FMT, a noncatecholic PET tracer for AAAD: 1) Where is the specific uptake of 6‐FMT? 2) Why does it accumulate where and to the degree that it does? 3) How does its uptake differ from that of fluoroDOPA globally? and 4) Does its regional uptake differ significantly from that of fluoroDOPA? High‐resolution PET scans were obtained in three rhesus monkeys using 6‐FMT and in two of them using fluoroDOPA. Anatomic distribution was analyzed visually and quantitative uptake of 6‐FMT was compared with published regional decarboxylase activity and monoamine neurotransmitter concentrations. In addition to high uptake in the dopamine‐rich striatal nuclei, there was specific uptake of 6‐FMT in brain regions which have little dopaminergic innervation but which have other amines in significant concentration. 6‐FMT uptake correlated best with regional AAAD activity (r = 0.97). It correlated slightly less well with the sum of catecholamine and indolamine neurotransmitter concentrations, but does not correlate with dopamine concentration. The uptake of 6‐FMT is greater than that of fluoroDOPA, with only slight differences in their regional distributions. Radiolabeled analogs of DOPA are often implicitly or explicitly regarded as tracers for presynaptic dopaminergic function. However, localization of these tracers more broadly includes many regions with relatively high concentrations of norepinephrine and serotonin. This may be especially important in diseases or experimental states in which dopaminergic neurons are selectively reduced, and may allow for the study of nondopaminergic neuronal systems in vivo with this tracer. Synapse 34:111–123, 1999.