Amyotrophic Lateral Sclerosis Disease Background

Introduction

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease of the motor system. It is classified as a type of motor neuron disease and is colloquially referred to as Lou Gehrig’s disease. It is a progressive neurodegenerative disorder that primarily involves motor neurons in the cerebral cortex, brainstem, and spinal cord. Most cases of ALS are sporadic (90 to 95%) but can also be familial (5 to 10%).

Amyotrophic Lateral Sclerosis_Disease Background

Epidemiology

ALS has an incidence of 0.6 to 3.8 per 100,000 person-years while its prevalence is 2.7 to 8.4 per 100,000 persons. The risk of developing ALS increases with age, with sporadic cases having a mean age of onset of 58 to 63 years old and familial cases having a mean age of onset of 43 to 52 years old. A 1.2 to 2:1 male to female ratio exists with ALS. However, this difference disappears with increasing age, men and women being equally affected. Although ALS affects all races and ethnic backgrounds, Whites and non-Hispanics are more likely to develop the disease. A study in Japan showed that the annual crude incidence rate adjusted for age and sex is 2.3 per 100,000 people, similar to western cohorts.  

Cognitive dysfunction occurs in 20 to 50% of cases, and 5 to 15% develop dementia usually of the frontotemporal type. There is currently no cure, and the mean duration of survival is 2 to 5 years without tracheostomy and ventilator support. Survival is dependent on several factors (eg clinical presentation, rate of disease progression, early onset of respiratory failure, and nutritional status).

Pathophysiology

The pathophysiology of amyotrophic lateral sclerosis involves motor neuron degeneration and death, with glial cells replacing the lost neurons. The disappearance of cortical motor cells leads to retrograde axonal loss and gliosis in the corticospinal tract. The spinal cord atrophies, the ventral roots become thin, and large myelinated fibers in the motor nerves decrease in number. The muscles affected show denervation atrophy and evidence of reinnervation. ALS with frontotemporal dementia (ALS-FTD) may include a loss of frontal or temporal cortical neurons. There is also a loss of non-motor neurons with axons contributing to the descending fronto-ponto-cerebelalr tract and reduced density of myelinated sensory fibers. Lastly, intracellular inclusions in degenerating neurons and glia are often reported in neuropathologic studies. 

Risk Factors

The risk factors for amyotrophic lateral sclerosis include advanced age, family history, cigarette smoking, genetic susceptibility (common Asian variants: SOD1, FUS, C9ORF7, TARDBP), environmental toxin exposure, and even military service.