MRI of the cervical spinal cord predicts respiratory dysfunction in ALS

Abstract

For patients with amyotrophic lateral sclerosis (ALS), the primary therapeutic goal is to minimize morbidity. Non-invasive ventilation improves survival. We aim to assess whether Magnetic Resonance Imaging (MRI) of the cervical spinal cord predicts the progression of respiratory disorders in ALS. Brain and spinal MRI was repeatedly performed in the SOD1G86R mouse model, in 40 patients and in healthy controls. Atrophy, iron overload, white matter diffusivity and neuronal loss were assessed. In Superoxide Dismutase-1 (SOD1) mice, iron accumulation appeared in the cervical spinal cord at symptom onset but disappeared with disease progression (after the onset of atrophy). In ALS patients, the volumes of the motor cortex and the medulla oblongata were already abnormally low at the time of diagnosis. Baseline diffusivity in the internal capsule was predictive of functional handicap. The decrease in cervical spinal cord volume from diagnosis to 3 months was predictive of the change in slow vital capacity at 12 months. MRI revealed marked abnormalities at the time of ALS diagnosis. Early atrophy of the cervical spinal cord may predict the progression of respiratory disorders, and so may be of value in patient care and as a primary endpoint in pilot neuroprotection studies.

Trial registration: ClinicalTrials.gov NCT02360891.

Conflict of interest statement

Véronique Danel, Jean Christophe Devedjian Guillaume Grolez, Kelly Timmerman, Maud Petrault, Charlotte Laloux, Renaud Lopes, Grégory Kuchcinski, Florent Auger, Alain Duhamel, Maeva Kyheng, Patrice Jissendi-Tchofo, Pierre François Pradat, Pierre Besson, Guillaume Grolez, Régis Bordet have no disclosures. Caroline Moreau has received various honoraria from pharmaceutical companies for consultancy and lectures on Parkinson’s disease at symposia such as Aguettant, Abbvie, Medtronic, Novartis. Luc Defebvre served on the Scientific Advisory Board for Novartis and Aguettant, and received honoraria from pharmaceutical companies for consultancy and lectures. David Devos served on advisory boards, as a consultant and given lectures for pharmaceutical companies such as Orkyn, Aguettant, Abbvie, Medtronic, Novartis, Teva, UCB, Lundbeck, ApoPharma.

Figures

Figure 1

MRI findings in SOD186R mice. MRI findings in SOD186R mice versus wild type mice (WT). *Means p < 0.05 (ANCOVA adjusted on the baseline values (i.e. Day 70)).