Energy dysfunction has been proposed as a key driver of axonal degeneration in MS. Diffusion-weighted ¹H magnetic resonance spectroscopy (DW-MRS) allows to measure the diffusivity of creatine-phosphocreatine (tCr), a tandem of metabolites involved in ATP production, whose reduction in the thalamus of patients with MS is thought to reflect a state of reduced energy supply of neurons and glial cells.

Seventeen patients with MS and thirteen healthy controls (HCs) underwent DW-MRS. From DW-MRS, tCr apparent diffusion coefficient ADC(tCr) was extracted in the thalami. Thalamo-cortical projections to somatosensory (SS) and dorsolateral prefrontal (DLPF) cortex, and optic radiations (OR) (all connected with thalamus), and the arcuate fasciculus (employed as control tract as not connected with thalamus) were manually drawn in TrackVis. Average mean (MD) diffusivity was extracted for each tract. The associations between thalamic ADC(tCr) and diffusion-based metrics of all tracts were assessed in patients and HCs using linear mixed-effect regression models.

Energy dysregulation of thalamic neurons and glial cells was associated with specific microstructural damage of thalamo-cortical projections in patients with MS. Our results suggest that reduced energy supply in this crucial hub, possibly resulting from an impaired transport/utilization of key intermediates in ATP-generating reactions, may disrupt thalamo-cortical networks inducing the selective anterograde structural degeneration of connected fibers.