Longitudinal study of the substantia nigra in Parkinson disease: A high-field (1) H-MR spectroscopy imaging study.

INTRODUCTION: The value of biomarkers in early diagnosis and development of therapeutics in Parkinson's disease (PD) is well established. METHODS: We used proton magnetic resonance spectroscopy in a prospective, longitudinal study of 23 patients with early PD, naïve to dopaminergic therapy, and six age-matched healthy controls to examine the temporal changes in metabolic profile of substantia nigra over a period of 3 months. RESULTS: N-acetyl aspartate to creatine ratio at month 3 was compared with baseline values in the PD and control groups, as well as the side-to-side difference of the ratio at baseline. By month 3, n-acetyl aspartate to creatine ratio had decreased by 4.4% in patients with PD (P = 0.024), without a concomitant change in healthy controls. The side-to-side asymmetry was significantly higher in the PD group (16.7%) vs. healthy controls (1.6%, P = 0.0024). CONCLUSION: Estimation of change in the n-acetyl aspartate to creatine ratio appears to be a fast, quantifiable, and reliable marker of dopaminergic neuronal viability in PD.

Characterization of retinal architecture in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder associated with dopaminergic cell loss and α-synuclein aggregation in Lewy bodies, which has been demonstrated in the retina. METHODS: We performed a spectral-domain optical coherence tomography (OCT) study in patients with PD and healthy controls to measure the peripapillary retinal nerve fiber layer thickness and macular volume. Intra-retinal segmentation was performed to measure the volume of the retinal nerve fiber (RNFL), ganglion cell (GCL), inner plexiform (IPL), inner nuclear (INL), outer plexiform (OPL), and outer nuclear (ONL) layers. Analysis was carried out blinded to the clinical status of study participants. RESULTS: 101 PD and 46 healthy control eyes were included in the study. In PD patients, peripapillary retinal nerve fiber layer was not significantly thinner (96.95 µm vs 94.42 µm, p=0.08) but macular volume was (8.58 mm3 vs 8.33 mm3, p=0.0002). Intra-retinal segmentation showed that PD subjects have reduced GCL, IPL, INL and ONL volumes. In contrast, the OPL volume was significantly increased (0.81 mm3 vs 0.78 mm3 p=0.0214). CONCLUSIONS: Thickening of the OPL is a novel finding which may correspond to the localization of α-synuclein in the OPL of PD patients. We hypothesize that the enlargement of the OPL may represent a potential biomarker of α-synuclein aggregation in PD. This may have significant clinical implications.