Heterogeneity of pathological processes in amyotrophic lateral sclerosis?

Challenges in the Understanding and Treatment of Amyotrophic Lateral Sclerosis/Motor Neuron Disease

“…Our inability to find effective therapeutics that fundamentally alter the disease course of ALS/MND is often attributed to this heterogeneity of the patient population; thus, there is a need for better diagnostic definitions that will allow for the prognostically relevant categorizations of the disease [3][4][5][7][8][9][10][11]. Our difficulty in identifying reliable biomarkers of disease progression and therapeutic benefit further confound this challenge [4,[12][13][14].…”

Measuring the progression of upper motor neuron disease using diffusion MRI and its correlation with Clinical phenotype

“…However, modern evidence supports the hypothesis that upper motor neurons are the site of the first pathology in ALS (Ishikawa, Nagura et al 1993, Vucic 2011, Devine, Pannek et al 2015 which is supported by our findings in this project. Autopsy studies of ALS clearly show that there is loss of upper and lower motor neurons and degeneration of the corticospinal tracts.…”

“…These authors suggested that this indicates that upper motor neuron degeneration occurs early in the disease which is clinically evident. Our previous study of clinical signs in ALS show that UMN degeneration also occurs early (Devine, Kiernan et al 2014), and neurophysiological studies of excitability also suggest that upper motor neuron degeneration occurs early (Vucic 2011). This could mean that changes in FA occur early in disease.…”

“…However, even though there was no significant change in DTI in the whole group, there was change in some patients and some correlation of rate of change in FA with survival (Vucic 2011). This could suggest that in those patients in whom change in FA is seen, this is a marker of progression.…”