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

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. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting upper and lower motor neurons, characterized by progressive muscle atrophy, paralysis and death. ALS is the most common motor neuron disease [1] affecting approximately 0.8-8.5 people per 100,000 worldwide [2]. While approximately 5% of cases are genetically linked (familial ALS), the majority of cases, 95%, are sporadic ALS with poorly understood etiologies. However, clinical presentation and pathology of sporadic and familial ALS are similar. The major risk factor for ALS is age, with the typical onset between 40 and 60 years of age [1]. Another risk factor of recent interest is trauma, specifically trauma to the brain and spinal cord. Epidemiological literature has reported a link between repeated head trauma and increased risk of ALS. Further, epidemiological Open Journal of Neuroscience