Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's Disease is a progressive upper and lower motor neuron disease that affects nerve cells in the brain and spinal cord, causing loss of muscle control.

• Approximately 5,000 people in the United States are diagnosed with ALS each year.
• Most people develop ALS between the ages of 40 to 70, with an average age of 55 at the time of diagnosis.

• As ALS progresses, muscle weakness and atrophy spreads to other parts of the body.
• Individuals may develop problems with motor movements, dysphagia, dysarthria, and dyspnea.
• Ultimately, patients eventually lose the ability to breathe on their own and will require assistance from a ventilator.

• The prevalence of dementia, parkinsonism, and depressive symptoms is significantly higher in the ALS.^[1]

• ALS is 20% more common in men than in women

• ALS is a clinical diagnosis based on the physical exam, history, and accompanying investigations. There is no definitive test for ALS, but diagnostic criteria are used to guide clinicians, including the Awaji criteria.^[2]

• Muscle fasciculations are often a first sign of ALS, though this can also occur in normal, healthy adults.

• Nearly all cases of ALS are considered sporadic, while the remaining 5 to 10% are familial (genetic)
• Between 25 to 40% of all familial cases (and a minority of sporadic cases) are caused by a mutation in the C9ORF72 gene which produces a protein that is found in motor neurons and nerve cells
  • This same genetic mutation is found in a subset of individuals with frontotemporal dementia, suggesting an overlapping pathophysiology in these two conditions.

• Both Primary Lateral Sclerosis (PLS) and Progressive Muscular Atrophy (PMA) are variants of ALS, and people with these disorders may progress to develop true ALS.
  • Primary Lateral Sclerosis (PLS)
    • A variant of ALS that affects only upper motor neurons. Individuals with PLS have spasticity (indicative of upper motor disease) that may affect their ability to articulate, swallow, or mobilize.
  • Progressive Muscular Atrophy (PMA)
    • Is a variant of ALS that affects only lower motor neurons, causing muscle weakness and atrophy.
• Spinal cord lesions
• Endocrine disorders
• Huntington's disease
• Muscular dystrophies
• Myasthenia gravis
• Polymyositis
• Multiple sclerosis

• Individuals with a strong family history should undergo genetic testing for gene mutations associated with ALS (e.g. - C9ORF72 mutation).
• Muscle biopsies may be performed to rule out other muscle disease other than ALS.
• Electromyography (EMG)
• Nerve conduction study (NCS)
• Magnetic resonance imaging (MRI)

• The neurologic examination should assess for motor weakness, atrophy, and spasticity.
• Atrophy of parts of the thenar eminence is an early clinical sign of ALS.^[3]