Longitudinal changes of cerebral glutathione (GSH) levels associated with the clinical course of disease progression in patients with secondary progressive multiple sclerosis

Abstract

Background: Increased oxidative stress leads to loss of glutathione (GSH). We have reported lower cerebral GSH in patients with secondary progressive multiple sclerosis (SPMS), indicating the involvement of oxidative stress in multiple sclerosis (MS) pathophysiology. Objective: This study expanded upon our earlier work by examining longitudinal changes in cerebral GSH in patients with SPMS in relation to their clinical status. Methods: A total of 13 patients with SPMS (Expanded Disability Status Scale (EDSS) = 4.0–6.5; MS duration = 21.2 ± 8.7 years) and 12 controls were studied over 3–5 years. GSH mapping was acquired from frontal and parietal regions using a multiple quantum chemical shift imaging technique at 3 T. Clinical assessments of the patient’s disability included EDSS, gait, motor strength, ataxia, tremor, brainstem function and vision changes. Results: Brain GSH concentrations in patients were lower than those in controls for both baseline and 3- to 5-year follow-ups. Longitudinal GSH changes of patients were associated with their neurologist’s blinded appraisal of their clinical progression. Patients judged to have worsening clinical status had significantly greater declines in frontal GSH concentrations than those with stable clinical status. Conclusion: GSH provides a distinct measure associated with the disease progression in SPMS, possibly due to its dynamic alignment with pathogenic processes of MS related to oxidative stress.