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


CONCLUSIONS
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.
Hoglund Brain Imaging Center and Departments of Molecular & Integrative Physiology and Neurology, University of Kansas Medical Center, Kansas City, KS, USA.
In-Young
IY
Choi
Hoglund Brain Imaging Center and Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA.
Phil
P
Lee
Department of Psychology, University of Kansas, Lawrence, KS, USA.
Abbey J
AJ
Hughes
Department of Psychology, University of Kansas, Lawrence, KS, USA.
Douglas R
DR
Denney
Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.
Sharon G
SG
Lynch
D015415:Biomarkers / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D016022:Case-Control Studies; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress; D013997:Time Factors
D015415:Biomarkers; D005978:Glutathione
Glutathione; chemical shift imaging; human brain; magnetic resonance spectroscopy; neurodegeneration; oxidative stress; secondary progressive multiple sclerosis