Neurological Disorders and Women's Health: Contribution of Molecular Neuroimaging Techniques.

Sex differences in brain physiology and the mechanisms of drug action have been extensively reported. These biological variances, from structure to hormonal and genetic aspects, can profoundly influence healthy functioning and disease mechanisms and might have implications for treatment and drug development. Molecular neuroimaging techniques may help to disclose sex's impact on brain functioning, as well as the neuropathological changes underpinning several diseases. This narrative review summarizes recent lines of evidence based on PET and SPECT imaging, highlighting sex differences in normal conditions and various neurological disorders.

Progressive Dopamine Transporter Binding Loss in Autopsy-Confirmed Corticobasal Degeneration.

BACKGROUND: Corticobasal degeneration (CBD) is characterized by neuronal and glial deposition of 4-repeat tau in the frontal and parietal cerebral cortex, white matter and striatum. There is neuronal loss in affected cortical regions and in the substantia nigra (SN). Recent single photon emission tomography (SPECT) studies have reported normal striatal dopamine transporter (DAT) binding in individual patients with CBD. OBJECTIVE: To study the pattern and course of DAT binding loss in CBD. METHODS: We retrospectively analyzed DAT SPECT studies in two patients presenting with a corticobasal syndrome in whom a diagnosis of CBD was later confirmed pathologically. RESULTS: Baseline scans at 1.5 years after symptom onset revealed only mild abnormalities (reduced uptake in one putamen). Follow up scans at 4.5 years (Case 1) and 5 years (Case 2) after symptom onset showed a marked decline of striatal DAT binding. In both cases, there was a 37% binding reduction from the age-expected striatal binding value. Asymmetry of striatal DAT binding had increased from mild in the first SPECT studies to moderate at the time of their final imaging. CONCLUSION: CBD patients can have delayed neuronal loss in the SN. Follow up DAT imaging may be of value in patients with possible CBD and a normal baseline scan.

Correlation of striatal dopamine transporter imaging with post mortem substantia nigra cell counts.

Dopamine transporter imaging is widely used for the differential diagnosis of parkinsonism. Only limited data are available on the relationship between striatal dopamine transporter binding and dopaminergic cell loss in the substantia nigra (SN). We analyzed postmortem SN cell counts in patients who had previously undergone dopamine transporter single-photon emission computed tomography (SPECT). Pathological diagnoses included Parkinson's disease (n = 1), dementia with Lewy bodies (n = 2), multiple system atrophy (n = 1), corticobasal degeneration (n = 2), atypical parkinsonism with multiple pathological conditions (n = 1), Alzheimer's disease (n = 1), and Creutzfeldt-Jakob disease (n = 1). [(12) (3) I]ß-CIT SPECT had been performed in all subjects using a standardized protocol on the same triple-head gamma camera. The density of neuromelanin-containing and tyrosine hydroxylase-positive substantia nigra neurons/mm(2) was evaluated in paraffin-embedded tissue sections by morphometric methods. Mean disease duration at the time of dopamine transporter imaging was 2.3 years, and the mean interval from imaging to death was 29.3 months (range, 4-68 months). Visual analysis of dopamine transporter images showed reduced striatal uptake in all seven patients with neurodegenerative parkinsonism, but not in Alzheimer's and Creutzfeldt-Jakob disease cases. Averaged [(right+left)/2] striatal uptake was highly correlated with averaged SN cell counts (rs = 0.98, P < 0.0005 for neuromelanin- and rs = 0.96, P < 0.0005 for tyrosine hydroxylase-positive cells). Similar strong correlations were found in separate analyses for the right and left sides. Striatal dopamine transporter binding highly correlated with postmortem SN cell counts, confirming the validity of dopamine transporter imaging as an excellent in vivo marker of nigrostriatal dopaminergic degeneration.

Dopamine D2 receptor SPECT in corticobasal syndrome and autopsy-confirmed corticobasal degeneration.

BACKGROUND: Corticobasal degeneration (CBD) is a rare neurodegenerative disorder characterized by tau-positive neuronal and glial lesions in the cortex and striatum with neuronal loss in cortical regions and in the substantia nigra. Striatal dopamine D2 receptor binding in autopsy-confirmed CBD has not been studied before. METHODS: We performed D2 receptor single photon emission computerized tomography using (123)I-IBZM in nine patients with a clinically diagnosed corticobasal syndrome (CBS) and on ten healthy controls. Two of the patients subsequently came to autopsy and were diagnosed with CBD. RESULTS: Overall striatal D2 receptor binding was preserved in 8/9 patients, but more asymmetric than in controls. Overall striatal binding in pathologically confirmed CBD was reduced in one case and normal in the other, and was lower contralateral to the clinically more affected side in both. CONCLUSION: This first study on D2 receptor imaging in autopsy-confirmed CBD demonstrates that loss of postsynaptic striatal neurons in CBD is a variable finding. Given the heterogeneity of our findings in pathology-confirmed cases, D2 receptor imaging seems to be of little practical value in the diagnostic workup of patients with CBS.