A Glimpse Into ALS Pathology
A Glimpse Into ALS Pathology
Ikawa M, Okazawa H, Tsujikawa T, et al
Neurology. 2015;84:2033-2039
Amyotrophic lateral sclerosis (ALS) has been linked to cerebral oxidative stress caused by mitochondrial dysfunction. The goal of this study was to investigate this phenomenon and its association with disease severity, using cerebral PET scanning with [Cu]diacetyl-bis(N-methylthiosemicarbazone), or Cu-ATSM, as a marker of oxidative stress. After a Cu-ATSM injection, 12 patients with ALS and nine age-matched healthy control participants underwent a 20-minute dynamic brain PET scan.
Statistical parametric mapping and region of interest analysis showed that compared with controls, patients with ALS had a significantly greater accumulation of Cu-ATSM in the bilateral cortices around the central sulcus, including the motor cortex, and the right superior parietal lobule. The investigators also looked at standardized uptake value (SUV) images taken from the last 10 minutes of PET scan frames and normalized by the global mean (nSUV). Increases in nSUV for the bilateral cortices around the central sulcus, including the motor cortex, and the right superior parietal lobule in patients with ALS were associated with decreases in the revised ALS Functional Rating Scale score, suggesting good correlation with ALS disease severity. In control participants, but not in patients with ALS, there was a correlation of age with nSUV for the bilateral cortices around the central sulcus.
In this study, Cu-ATSM PET imaging in patients with ALS showed increased oxidative stress based on an overreductive state, mostly in the motor cortex. The good correlation of magnitude of oxidative stress with clinical severity suggests its potential association with neurodegenerative changes in ALS. However, limitations of this study include its small sample size and its cross-sectional design, which precludes determination of causality.
In an accompanying commentary, Peter J. Crouch noted that the study supports the use of Cu-ATSM to image ALS with PET scanning. He suggested that increasing the radioactive half-life of the tracer by using Cu-ATSM (12 hours) instead of Cu-ATSM (10 minutes), while using a longer postinjection imaging interval, may improve sensitivity and help determine whether Cu-ATSM PET could be used as a diagnostic tool in ALS.
Abstract
Increased Oxidative Stress Is Related to Disease Severity in the ALS Motor Cortex: A PET Study
Ikawa M, Okazawa H, Tsujikawa T, et al
Neurology. 2015;84:2033-2039
Study Summary
Amyotrophic lateral sclerosis (ALS) has been linked to cerebral oxidative stress caused by mitochondrial dysfunction. The goal of this study was to investigate this phenomenon and its association with disease severity, using cerebral PET scanning with [Cu]diacetyl-bis(N-methylthiosemicarbazone), or Cu-ATSM, as a marker of oxidative stress. After a Cu-ATSM injection, 12 patients with ALS and nine age-matched healthy control participants underwent a 20-minute dynamic brain PET scan.
Statistical parametric mapping and region of interest analysis showed that compared with controls, patients with ALS had a significantly greater accumulation of Cu-ATSM in the bilateral cortices around the central sulcus, including the motor cortex, and the right superior parietal lobule. The investigators also looked at standardized uptake value (SUV) images taken from the last 10 minutes of PET scan frames and normalized by the global mean (nSUV). Increases in nSUV for the bilateral cortices around the central sulcus, including the motor cortex, and the right superior parietal lobule in patients with ALS were associated with decreases in the revised ALS Functional Rating Scale score, suggesting good correlation with ALS disease severity. In control participants, but not in patients with ALS, there was a correlation of age with nSUV for the bilateral cortices around the central sulcus.
Viewpoint
In this study, Cu-ATSM PET imaging in patients with ALS showed increased oxidative stress based on an overreductive state, mostly in the motor cortex. The good correlation of magnitude of oxidative stress with clinical severity suggests its potential association with neurodegenerative changes in ALS. However, limitations of this study include its small sample size and its cross-sectional design, which precludes determination of causality.
In an accompanying commentary, Peter J. Crouch noted that the study supports the use of Cu-ATSM to image ALS with PET scanning. He suggested that increasing the radioactive half-life of the tracer by using Cu-ATSM (12 hours) instead of Cu-ATSM (10 minutes), while using a longer postinjection imaging interval, may improve sensitivity and help determine whether Cu-ATSM PET could be used as a diagnostic tool in ALS.
Abstract