To assess the brain ¹⁸F-FDG-PET metabolic changes related to King’s stages in ALS.

Pathological studies have supported the concept of ALS spreading by corticofugal propagation. The King’s staging system (KSS) reflects the extent of involvement in different body regions, and represents a proxy of the diffusion of lesions in the CNS in ALS.

A total of 390 ALS cases with KSS 1, 2 or 3 seen at the ALS Centre of Turin, Italy, in the period 2008-2015 underwent brain ¹⁸F-FDG-PET at diagnosis. KSS was regressed against brain metabolism using the multiple regression model of SPM 12. Two-sample t-test was used for group comparisons. Age at PET and sex were included as covariates in all the analyses (height threshold p<0.001; p<0.05 FWE_corrected at cluster level).

In the multiple regression analysis brain metabolism correlated negatively with KSS (KSS 1, relatively highest metabolism; KSS 3, relatively lowest metabolism) in bilateral medial frontal gyrus (BA6), right precentral gyrus (BA4), and right postcentral gyrus (BA2). No significant positive correlation (hypermetabolic areas) was found. The comparison between the group with KSS 1 and the group with KSS2 revealed no significant difference. Comparing KSS 1+2 vs KSS 3 we found a significant relative hypometabolism in the KSS 3 group in left precentral and medial frontal gyrus (BAs 4 and 6), and right precentral, middle frontal, postcentral, and medial frontal gyrus (BAs 4, 6, 3, 9, and 8). No clusters of relative hypermetabolism were found.

With the increase of KSS, we found a decreasing gradient of metabolism in motor areas, with the involment of extramotor regions. Our findings support the hypothesis that that the neurodegenerative process of ALS tends to spread from the motor cortex to posterior and anterior regions in an ordinate sequence.