Brain and Spinal Cord Trauma as a Risk Factor for Amyotrophic Lateral Sclerosis: A Mini-Review

Abstract

Trauma to the central nervous system (CNS) has been investigated as a risk factor for amyotrophic lateral sclerosis (ALS) despite conflicting epidemiological reports. Studies have suggested a link between ALS and traumatic axonal injury which complements the “dying back” theory of ALS. The theory suggests that neuronal dysfunction first occurs at the neuromuscular junction, and subsequent axonal impairment leads to dysfunction of the cell body. A pathological link has been shown between CNS trauma and ALS, further supporting this relationship. Another proposed hypothesis is that differences in “molecular thresholds” based on individual genetic backgrounds could explain some individuals developing ALS or ALS-like pathology subsequent to trauma, as well as elucidate the seemingly increased risk for ALS associated with multiple traumas. However, it is still unclear how trauma to the CNS might directly or indirectly trigger ALS. The current minireview re-examines the relationship between CNS trauma and risk of developing ALS or an ALS-like pathology, and explores potential explanations for discrepant study results.