Neuromuscular electrical stimulation and dietary interventions to reduce oxidative stress in a secondary progressive multiple sclerosis patient leads to marked gains in function: a case report

Background: Disability levels for patients with secondary progressive multiple sclerosis (SPMS) often worsen despite a stable MRI T2 lesion burden. The presence of oxidative stress in the absence of measurable inflammation could help explain this phenomenon. In this study, the assessment of an in vivo marker of oxidative stress, cerebral glutathione (GSH), using magnetic resonance chemical shift imaging (CSI) is described, and GSH levels were compared in patients with SPMS and healthy controls. Objective: To assess whether GSH, a key antioxidant in the brain, is lower in the SPMS patients compared to matched controls. Methods: Seventeen patients with SPMS (Expanded Disability Status Scale = 4.0–7.0; length of MS diagnosis = 19.4 ± 7 years) and 17 age- and gender-matched healthy controls were studied. GSH levels were measured in the fronto-parietal regions of the brain using a specially designed magnetic resonance spectroscopy technique, CSI of GSH, at 3T. Results: The levels of GSH were lower for SPMS patients than for controls, the largest reduction (18.5%) being in the frontal region ( p = 0.001). Conclusion: The lower GSH levels in these patients indicate the presence of oxidative stress in SPMS. This process could be at least partially responsible for ongoing functional decline in SPMS.

Download Full-text

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

Multiple Sclerosis Journal ◽

10.1177/1352458516669441 ◽

2016 ◽

Vol 23 (7) ◽

pp. 956-962 ◽

Cited By ~ 8

Author(s):

In-Young Choi ◽

Phil Lee ◽

Abbey J Hughes ◽

Douglas R Denney ◽

Sharon G Lynch

Keyword(s):

Oxidative Stress ◽

Multiple Sclerosis ◽

Disease Progression ◽

Clinical Status ◽

Progressive Multiple Sclerosis ◽

Secondary Progressive Multiple Sclerosis ◽

Multiple Quantum ◽

Longitudinal Changes ◽

Secondary Progressive ◽

Motor Strength

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.

Download Full-text