Cord cross-sectional area at foramen magnum as a correlate of disability in amyotrophic lateral sclerosis

Spinal cord atrophy is one of the hallmarks of amyotrophic lateral sclerosis (ALS); however, it is not routinely assessed in routine clinical practice. In the present study, we evaluated whether spinal cord cross-sectional area measured at the foramen magnum level using a magnetic resonance imaging head scan represents a clinically meaningful measure to be added to the whole-brain volume assessment. Using an active surface approach, we measured the cord area at the foramen magnum and brain parenchymal fraction on T1-weighted three-dimensional spoiled gradient recalled head scans in two groups of subjects: 23 patients with ALS (males/females, 13/10; mean ± standard deviation [SD] age 61.7 ± 10.3 years; median ALS Functional Rating Scale–Revised score 39, range 27–46) and 18 age- and sex-matched healthy volunteers (mean ± SD age 55.7 ± 10.2 years). Spinal cord area at the foramen magnum was significantly less in patients than in control subjects and was significantly correlated with disability as measured with the ALS Functional Rating Scale–Revised (ρ = 0.593, p <  0.005). This correlation remained significant after taking into account inter-individual differences in brain parenchymal fraction (ρ = 0.684, p <  0.001). Our data show that spinal cord area at the foramen magnum correlates with disability in ALS independently of whole-brain atrophy, thus indicating its potential as a disease biomarker.