Amyotrophic Lateral Sclerosis: A Predominant Form of Degenerative Disease of the Motor Neuron System

Background

ALS is a clinically and genetically heterogeneous, devastating, rapidly progressive neurodegenerative motor disorder with cognitive and behavioral impairments as core features (Schmidt et al, 2016). Alongside behavioral features, executive dysfunction is present in up to 50% of ALS patients (Beeldman et al, 2016). Anatomical connectivity studies have revealed clear white matter impairments, mostly affecting tracts directly linked to the motor cortex (Schmidt et al, 2014).

Improvements in our knowledge of the glutamate neurotransmitter system coupled with the detection of causal genes associated with the progression of familial ALS (fALS) have inspired research interest (Kiernan et al, 2011). Whereas these research findings allow for vital comprehensions regarding the ultimate consequences of ALS on the brain, the causal pathogenic mechanism of ALS remains largely unknown (Schmidt et al, 2016).

Cronin et al (2007) reported that there is a low incidence of ALS in people with mixed ancestral origin than in people of Spanish origin. About 5–10% of ALS is familial, with a Mendelian pattern of inheritance. The remaining 90% of the ALS population is identified as having sporadic disease for which results from family aggregation studies have realized a connection between ALS and common NDs, indicative of the presence of susceptibility genes that might elevate the overall risk of neurodegeneration among relatives (Fallis & Hardiman, 2009). As such, attempts to identify susceptibility genes have had little influence on the establishment of a complex genetic basis for sporadic ALS.