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A 66-year-old woman complained of a 3-year history of left ankle focal spasticity. Brain MRI revealed subcortical white matter hyperintensity in the medial region of the right precentral gyrus. Subsequently, motor impairment spread proximally, to the contralateral lower limb and then to ipsilateral arm, ultimately resulting in a progressive asymmetric tetraparesis and a mild dysarthria. After a 4-year follow-up, a diagnosis of definite primary lateral sclerosis was established.1 Clinical progression was mirrored by corresponding spreading of the MRI hyperintensity through motor areas (Figure, A) and extensive microstructural damage of the corticospinal tract shown by diffusion tensor MRI tractography (Figure, B), consistently with a model of TDP-43 protein prion-like transmission through the complex 3D anatomy of the motor system.2
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