Targeted assessment of lower motor neuron burden is associated with survival in amyotrophic lateral sclerosis

Abstract

Estimating survival in amyotrophic lateral sclerosis (ALS) is challenging due to heterogeneity in clinical features of disease and a lack of suitable markers that predict survival. Our aim was to determine whether scoring of upper or lower motor neuron weakness is associated with survival. With this objective, 161 ALS subjects were recruited from two tertiary referral centres. Scoring of upper (UMN) and lower motor neuron (LMN) signs was performed, in addition to a brief questionnaire. Subjects were then followed until the censorship date. Univariate analysis was performed to identify variables associated with survival to either non-invasive ventilation (NIV) or death, which were then further characterized using Cox regression. Results showed that factors associated with reduced survival included older age, bulbar and respiratory involvement and shorter diagnostic delay (all p < 0.05). Whole body LMN score was strongly associated with time to NIV or death (p ≤0.001) whereas UMN scores were poorly associated with survival. In conclusion, our results suggest that, early in disease assessment and in the context of other factors (age, bulbar, respiratory status), the burden of LMN weakness provides an accurate estimate of outcome. Such a scoring system could predict prognosis, and thereby aid in selection of patients for clinical trials.

Assessment of Motor Units in Neuromuscular Disease

“…Patients with ALS have differing rates of disease progression and while average survival is typically 2-3 years, a tail of long survivors occurs, partly due to disease pathology and also due to patient choices regarding respiratory support [88]. The severity of lower motor neuron involvement in ALS appears to be particularly relevant for survival [92], and therefore is an important measure to be evaluated in clinical trials.…”

Energy metabolism in amyotrophic lateral sclerosis: assessment of body composition and energy expenditure

“…Older age and bulbar involvement at disease onset (Chiò et al, 2009), cognitive impairment (Elamin et al, 2011), LMN dysfunction (Devine et al, 2016) and respiratory muscle weakness (Pinto et al) predict a shorter survival time. There are also some genes that modify the clinical course of ALS (Meyer et al, 2005, Fogh et al, 2016, Lopez-Lopez et al, 2014, Taylor et al, 2016.…”

“…The original authors of this grading system used it to demonstrate the focality of upper and lower motor neurone degeneration in ALS . It has subsequently been used to show that LMN burden is associated with survival in ALS (Devine et al, 2016).…”

“…Scores from each limb were summed to give a total UMN and LMN score, each out of 12. (Devine et al, 2016) and .…”

“…The physical examination performed by the neurologist at the RBWH MND clinic at the time of ALS diagnosis was used to determine the upper motor neurone (UMN) and lower motor neurone (LMN) score as previously described , Devine et al, 2016 (Table 3.1). Each limb was given an UMN and LMN score from 0-3 based on the degree of hyper-reflexia, spasticity and clonus, or degree of wasting and weakness respectively.…”