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]
Risk Factors
  • 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
  • Muscular dystrophies
  • Myasthenia gravis
  • Polymyositis
  • 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]
For Patients
For Providers