28.: Asymmetry of motor dysfunction in amyotrophic lateral sclerosis: The effect of limb dominance

Abstract

In amyotrophic lateral sclerosis (ALS), onset and spread of upper (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, and to further explore any findings using imaging. We initially 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. A separate cohort of 15 right-dominant ALS subjects, with onset of limb weakness on the dominant side, were also studied using a voxel-based morphometry asymmetry analysis protocol applied to structural brain MRI, and compared with 15 age and sex-matched controls. 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). Compared with matched controls, right-dominant subjects with ALS showed disproportionate loss of gray matter density in the left (dominant) hemisphere hand representation area (p