Amyotrophic Lateral Sclerosis (ALS)

Primer

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.

Epidemiology
  • 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.
Prognosis
  • 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.
Comorbidity
  • 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

Diagnosis

  • 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]

Signs and Symptoms

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

Pathophysiology

  • 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.

Differential Diagnosis

  • 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

Investigations

  • 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)

Physical Exam

  • 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]

Treatment

Guidelines

Resources

For Patients
For Providers
Articles
Research

References

1) Körner, S., Kollewe, K., Ilsemann, J., Müller‐Heine, A., Dengler, R., Krampfl, K., & Petri, S. (2013). Prevalence and prognostic impact of comorbidities in amyotrophic lateral sclerosis. European journal of neurology, 20(4), 647-654.
2) Costa, J., Swash, M., & de Carvalho, M. (2012). Awaji criteria for the diagnosis of amyotrophic lateral sclerosis: a systematic review. Archives of neurology, 69(11), 1410-1416.
3) Shibuya, K., Misawa, S., Nasu, S., Sekiguchi, Y., Mitsuma, S., Beppu, M., ... & Kuwabara, S. (2013). Split hand syndrome in amyotrophic lateral sclerosis: different excitability changes in the thenar and hypothenar motor axons. Journal of Neurology, Neurosurgery & Psychiatry, 84(9), 969-972.