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

Niccolò Piaggio,Carlo Scialò,Corrado Cabona,Claudia Caponnetto,Matteo Pardini,Giovanni L Mancardi,Laura Bonzano,Matilde Inglese,Luca Roccatagliata

doi:10.1186/s41747-018-0045-6

Abstract

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.

Highlights

Amyotrophic lateral sclerosis (ALS) is a degenerative disease involving both upper and lower motor neurons and leads to a fatal outcome in a variably short period of time
foramen magnum cord area (FMCA), C2-C3 area, and brain parenchymal fraction (BPF) values appeared normally distributed in the patients with ALS and the healthy control subjects
Overall, our findings show that FMCA as well as C2-C3 cord area correlates with clinical disability and that the correlation between FMCA and clinical disability score is independent of brain atrophy

Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is a degenerative disease involving both upper and lower motor neurons and leads to a fatal outcome in a variably short period of time (median survival 3 years). After an insidious and non-specific onset, the patient experiences progressively worsening functional deficits, such as weakness; fatigue; muscle atrophy; and, as the diseases progresses, loss of control of respiratory muscles, which is the major cause of mortality [1]. Several neuroprotective agents and neuroregenerative approaches are currently under study, and their efficacy is being assessed with functional tests, clinical scales and survival rates. Magnetic resonance imaging (MRI) of both brain and spinal cord in ALS [2] offers potentially valuable noninvasive radiological surrogate biomarkers at levels of both the whole brain and the region-of-interest [3]. Different studies showed a significant relationship of disability with MRI metrics of spinal cord damage, such as diffusion MRI [2, 5], and with cervical cord volume loss, usually assessed at the C2-C3 level [6]

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