Involvement of spinal sensory pathway in ALS and specificity of cord atrophy to lower motor neuron degeneration

Abstract

Our objective was to demonstrate that ALS patients have sensory pathway involvement and that local cord atrophy reflects segmental lower motor neuron involvement. Twenty-nine ALS patients with spinal onset and twenty-one healthy controls were recruited. Diffusion tensor imaging (DTI), magnetization transfer and atrophy index were measured in the spinal cord, complemented with transcranial magnetic stimulations. Metrics were quantified within the lateral corticospinal and the dorsal segments of the cervical cord. Significant differences were detected between patients and controls for DTI and magnetization transfer metrics in the lateral and dorsal segments of the spinal cord. Fractional anisotropy correlated with ALSFRS-R (p = 0.04) and motor threshold (p = 0.02). Stepwise linear regression detected local spinal cord atrophy associated with weakness in the corresponding muscle territory, i.e. C4 level for deltoid and C7 level for hand muscles. In conclusion, impairment of spinal sensory pathways was detected at an early stage of the disease. Our data also demonstrate an association between muscle deficits and local spinal cord atrophy, suggesting that atrophy is a sensitive biomarker for lower motor neurons degeneration.

Key words::

• ALS
• spinal cord
• diffusion tensor imaging
• magnetization transfer
• atrophy

Acknowledgements

We thank Kevin Nigaud, Alexandre Vignaud and Eric Bardinet for helping with the acquisition and Henrik Lundell for providing the code to measure the cord area. We are grateful for the contribution of the patients and their relatives. We thank the clinicians of the Paris ALS Centre, Gaëlle Bruneteau, Lucette Lacomblez, Marie-Violaine Lebouteux, Timothee Lenglet and François Salachas. We thank the reviewers for their very insightful comments. This study was supported by the Association Française contre les Myopathies (AFM), the Institut pour la Recherche sur la Moelle épinière et l'Encéphale (IRME), the National MS Society and the SensoriMotor Rehabilitation Research Team (SMRRT) of the Canadian Institute of Health Research.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.