Increased oxidative stress is related to disease severity in the ALS motor cortex

Objective: To investigate cerebral oxidative stress based on an over-reductive state caused by mitochondrial dysfunction and its relationship to disease severity in patients with amyotrophic lateral sclerosis (ALS) using PET with [⁶²Cu]diacetyl-bis(N⁴-methylthiosemicarbazone) (⁶²Cu-ATSM).

Methods: Twelve patients with ALS and 9 age-matched healthy controls underwent a 20-minute dynamic brain PET scan after ⁶²Cu-ATSM injection. The standardized uptake value (SUV) images obtained from the last 10 minutes of frames were normalized by the global mean (nSUV). Regional ⁶²Cu-ATSM retention in the nSUV images was compared between groups using statistical parametric mapping (SPM) and region of interest (ROI) analysis. Secondary analyses evaluated the correlations between regional nSUVs and the clinical characteristics of the participants.

Results: In SPM mapping, patients with ALS showed a significantly greater accumulation of ⁶²Cu-ATSM compared to controls in the bilateral cortices around the central sulcus, including the motor cortex, and the right superior parietal lobule. ROI analysis also revealed significantly greater nSUVs in patients than controls in these regions. Increases in nSUV for these regions were associated with decreases in the revised ALS Functional Rating Scale score, suggesting a good correlation with the severity of ALS. In controls, age was correlated with nSUV for the bilateral cortices around the central sulcus, although this correlation was not observed in patients with ALS.

Conclusions: ⁶²Cu-ATSM PET imaging demonstrated increased oxidative stress based on an over-reductive state, primarily in the motor cortex, in patients with ALS. The magnitude of oxidative stress correlated well with clinical severity, indicating that it may be associated with neurodegenerative changes in ALS.