Objective This study aimed to determine if the antioxidant N-acetylcysteine (NAC) is able to alter peripheral and central redox capabilities in patients with Parkinson disease (PD) or Gaucher disease (GD). Methods The study included nondemented adult subjects: 3 with PD, 3 with GD, and 3 healthy controls. Baseline brain glutathione (GSH) concentrations were measured using 7-T magnetic resonance spectroscopy (MRS). Baseline blood reduced-to-oxidized GSH ratios were determined for each subject. Brain GSH concentrations and blood redox ratios were then determined during and at specified time points after a single, 150-mg/kg NAC infusion. Results N-acetylcysteine increased blood GSH redox ratios in those with PD and GD and healthy controls, which was followed by an increase in brain GSH concentrations in all subjects. Conclusions This is the first demonstration that with MRS, it is possible to directly measure and monitor increases in brain GSH levels in the human brain in response to a single, intravenous administration of NAC. This work shows the potential utility of MRS monitoring, which could assist in determining dosing regimens for clinical trials of this potentially useful antioxidant therapy for PD disease, GD, and other neurodegenerative disorders.

Precise knowledge about limb position and orientation is essential for the ability of the nervous system to plan and control voluntary movement. While it is well established that proprioceptive signals from peripheral receptors are necessary for sensing limb position and motion, it is less clear which supraspinal structures mediate the signals that ultimately lead to the conscious awareness of limb position (kinaesthesia). Recent functional imaging studies have revealed that the cerebellum, but not the basal ganglia, are involved in sensory processing of proprioceptive information induced by passive and active movements. Yet psychophysical studies have suggested a prominent role of the basal ganglia in kinaesthesia. This study addresses this apparent dichotomy by investigating the contributions of the cerebellum and the basal ganglia to the perception of limb position. Using a passive movement task, we examined the elbow position sense in patients with a dysfunction of the basal ganglia (Parkinson’s disease, n = 9), patients with cerebellar degeneration [spinocerebellar ataxia (SCA) types 6 and 8, n = 6] and age‐matched healthy control subjects (n = 11). In comparison with healthy control subjects, Parkinson’s disease patients, but not SCA patients, were significantly impaired in the ability to detect displacements correctly. A 1° forearm displacement was correctly recognized in >75% of trials by control subjects and SCA patients, but only in 55% of Parkinson’s disease patients. Only at 6° displacement did Parkinson’s disease patients exhibit a response rate similar to those of the two other groups. Thresholds for 75% correct responses were 1.03° for controls, 1.15° for cerebellar patients and 2.10° for Parkinson’s disease patients. This kinaesthetic impairment significantly correlated with the severity of disease in Parkinson’s disease patients, as determined by the Unified Parkinson’s Disease Rating Scale (r = –0.7, P = 0.03) and duration of disease (r = –0.7, P = 0.05). In contrast, there was no significant correlation between performance and the daily levodopa equivalent dose. These results imply that an intact cerebro‐basal ganglia loop is essential for awareness of limb position and suggest a selective role of the basal ganglia but not the cerebellum in kinaesthesia.

BACKGROUND AND PURPOSE: Parkinson disease (PD) is characterized by basal ganglia abnormalities. However, there are neurodegenerative changes in PD that extend beyond the basal ganglia and that are not sufficiently evaluated with standard MR imaging. The aim of this study was to characterize whole-brain gray matter (GM) and white matter (WM) changes in PD by using diffusion tensor imaging (DTI).