In vivo mapping of sodium homeostasis disturbances in individual ALS patients: A brain 23Na MRI study

Objective Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by significant heterogeneity among patients. ²³Na MRI maps abnormal sodium homeostasis that reflects metabolic alterations and energetic failure contributing to the neurodegenerative process. In this study, we investigated disease severity at the individual level in ALS patients using brain ²³Na MRI. Methods ¹H and²³Na brain MRI were collected prospectively from 28 ALS patients. Individual map of abnormal total sodium concentration (TSC) was computed using voxel-based statistical mapping for each patient compared to a local database of 62 healthy controls. Clinical data included the revised ALS functional rating scale (ALSFRS-R), ALSFRS-R slope, ALSFRS-R at 6-month and survival time. Results Individual maps quantifying voxels with TSC increase evidenced a high heterogeneity between patients consistent with clinical presentation. The main areas involved were the corticospinal tracts. Half of patients showed abnormal TSC increase within more than 1% of whole brain voxels. Patients with TSC increase had worse clinical severity: higher ALSFRS-R slope (p = 0.02), lower ALSFRS-R at 6-month (p = 0.04), and shorter survival (p = 0.04). ALS patients with limited TSC increase had slower progression of disability or predominant lower motor neuron phenotype or shorter disease duration. Discussion This study mapping sodium homeostasis disturbances at the individual level in ALS patients through ²³Na MRI evidenced heterogeneity of TSC increase among patients associated with clinical presentation and disease severity. These findings suggest that TSC increase detected at the individual level by ²³Na MRI may be a useful marker of the clinical heterogeneity of ALS patients, a factor that is likely to greatly influence the results of therapeutic trials.