KD is a rare X-linked neurodegenerative disorder mainly affecting the lower motor neurons. Differential diagnosis from amyotrophic lateral sclerosis (ALS) and, particularly, lower motor neuron-predominant disease (LMND) might be challenging. The extent of central nervous system involvement relative to other MND phenotypes still needs to be clarified.

To investigate cortical and white matter (WM) alterations in a sizeable sample of patients with Kennedy’s disease (KD).

Subjects were prospectively enrolled between October 2009 and April 2016. Twenty-five KD patients were compared with 24 healthy subjects, 25 patients with amyotrophic lateral sclerosis (ALS), and 35 with lower motor neuron-predominant disease (LMND). LMND patients were clinically differentiated into 24 fast and 11 slow progressors. All subjects underwent T1-weighted and diffusion tensor (DT) MRI. Whole-brain cortical thickness, WM tract-based spatial statistics, and tractography of the corticospinal tract (CST) were performed. CST measures were compared by using analysis of variance.

No significant difference in terms of cortical thickness was found between groups. ALS patients showed widespread decreased fractional anisotropy and increased mean (MD) and radial diffusivity (radD) in the CST, corpus callosum and fronto-temporal extra-motor tracts, compared with healthy controls and other patient groups. CST tractography showed significant alterations of DT MRI metrics in ALS and LMND-fast patients whereas KD and LMND-slow patients were comparable with healthy controls. LMND-fast patients also showed a nearly-significant (p=0.06) increase in MD values of the right CST and radD values of the left CST relative to KD.

Our study demonstrated the absence of WM abnormalities in patients with KD and LMND-slow, in contrast with diffuse WM damage in ALS and focal CST degeneration in LMND-fast. These results support the use of DT MRI measures as powerful tools to differentiate fast- and slow-progressing MND syndromes, including KD.