Description

• Average survival ranges from 2 to 5 years from the time of diagnosis.
• >50% live >3 years, 25% live >5 years, 10% live >10 years, 5% live up to 20 years
• Sporadic ALS form is 90–95% of all cases. It includes a number of overlapping syndromes, such as pseudobulbar palsy, progressive bulbar palsy, progressive muscular atrophy, and primary lateral sclerosis.
• Familial ALS (FALS) is most commonly inherited as an autosomal dominant condition and less so as an autosomal recessive disease. This is clinically similar to sporadic ALS but probably represents a distinct entity pathologically and biochemically.
• Guam ALS and Parkinson-dementia complex are ALS-like syndromes often, but not always, associated with Parkinson syndrome and dementia. Guam ALS is prevalent among the Chamorro Indians of Guam and rare in the United States.
• System(s) affected: nervous
• Synonym(s): motor neuron disease (MND); Lou Gehrig disease; Charcot disease; ALS

Pregnancy Considerations

• Uncommon among affected individuals
• If pregnancy did occur, the only foreseeable difficulties would be related to weakness.

Epidemiology

Incidence

• In United States, 5,000 newly diagnosed per year
• Rate = 2 to 5/100,000 per year

Prevalence

• Estimated 20,000 Americans may have the disease at any given time without socioeconomic boundaries.
• ALS is more common among white males, non-Hispanics, and persons aged 60 to 69 years (1).
• Peak age onset of 58 to 63 years old for sporadic
• Peak age onset 47 to 52 years old for familial
• Predominant age: 40 to 70 years, average age 55 years old
• Predominant sex: male > female in sporadic ALS:
  • After 70 years and in FALS: male = female

Etiology and Pathophysiology

• Sporadic ALS: unknown cause, but elevated levels of glutamate have been found in serum and CSF
• FALS: neurodegenerative disease passed on directly or indirectly by skipping generation (2)
• Guam ALS and Parkinson-dementia complex: caused by eating bats that feed on cycad seeds (high concentration of neurotoxic amino acid)
• Degeneration of the UMNs/LMNs with gliosis replacing lost neurons; leads to spinal cord atrophy, thin ventral roots, and loss of large myelinated fibers in motor nerves
• Progressive weakness of both skeletal and smooth muscles that leads to progressive loss of function related to movement, speech, swallowing, and breathing

Genetics

• FALS, most common (5–10% of cases); can be autosomal dominant or autosomal recessive; X-linked dominant cases have been reported. 50–60% of FALS will have a detectable known genetic mutation.
• C9orf72 repeat expansions found in 2011 in 30–40% of FALS
• Gene locus has been localized to the long arm of chromosome 21 at position 22.11 and encodes the superoxide dismutase (SOD1) enzyme. This accounts for 15–20% of FALS cases and 5% of sporadic cases.
• FIG4 gene accounts for 3% of FALS.
• Mutations in several genes, including fused in sarcoma (FUS), angiogenin gene (ANG, encodes for angiogenin and ribonuclease), TAR DNA-binding protein (TARDBP), and TDP-43 (helps regulate transcription and alternative splicing), have been discovered to be associated with familial and sporadic ALS.
• Overall, 22 mutations have been reported with current research continuing to discover new genes associated with ALS.

Risk Factors

• Family history
• Age >40 years and <70 years
• Smoking
• Maternal age and increased number of younger siblings each may be associated with risk for ALS.
• Formaldehyde exposure (but not pesticide/herbicide exposure)
• Military personnel, due to environmental exposures

General Prevention

Genetic counseling is advised if there is a family history of ALS; however, sporadic ALS is not associated with genetic transmission.