Study of motor asymmetry in ALS indicates an effect of limb dominance on onset and spread of weakness, and an important role for upper motor neurons

Abstract

In amyotrophic lateral sclerosis (ALS), onset and spread of upper motor neuron (UMN) and lower motor neuron (LMN) dysfunction is typically asymmetric. Our aim was to investigate the relationship between limb dominance and the onset and spread of clinical UMN and LMN dysfunction in ALS. We studied 138 ALS subjects with unilateral and concordant limb dominance, from two tertiary centres. A questionnaire was used to determine the pattern of disease onset and spread. The clinical severity of UMN and LMN signs in each limb was quantified using a validated scoring system. Results showed that onset of weakness was more likely to occur in the dominant upper limb (p = 0.02). In subjects with initial weakness in a non-dominant limb, spread of weakness was more likely to be to the other limb on that side (p = 0.008). The relative distribution of upper limb UMN signs was affected by whether weakness first occurred on the dominant or non-dominant side (p = 0.03). These findings support limb dominance as a significant factor underlying onset and spread of ALS, with UMN processes playing an important role. The effect of limb dominance on the presentation of ALS may reflect underlying neuronal vulnerabilities, which become exposed by the disease.

Key words::

• Amyotrophic lateral sclerosis
• anterior horn cell disease
• motor neuron disease
• handedness
• limb dominance

Acknowledgements

We would like to acknowledge the assistance of Helen Woodhouse and Nicole Hutchinson (Royal Brisbane and Women's Hospital), Casey Pfluger (University of Queensland) and Eleanor Ramsey (Prince of Wales Hospital). We also acknowledge the statistical advice provided by Peter O’Rourke (Queensland Institute of Medical Research).

Conduct of this study was funded by the Motor Neuron Disease Research Fund, held with the Royal Brisbane and Women's Hospital Foundation. M.S. Devine was also supported by a research scholarship from the University of Queensland.

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