Amyotrophic Lateral Sclerosis (ALS)

Epidemiology

  • Peak Incidence: age 50-70
  • Race: occurs in all races and ethnic groups
  • Sex: M>F

Etiology

  • Sporadic ALS: 90-95% of cases
    • Family members are not at increased risk for ALS
  • Familial ALS: 5-10% of cases
    • 20% of familial cases result from superoxide dismutase 1 (SOD1) enzyme gene mutation

Physiology

  • Anterior horn motoneuron disease
    • Bilateral diaphragmatic paresis or paralysis (may occur in absence of periph-eral weakness in some ALS cases)
    • Pulmonary Hypertension: may occur due to neuromuscular disease with hypoventilation (leads to hypoxia and acidosis, with resultant pulmonary vasoconstriction)

Pathology

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Diagnosis

  • ABG: hypoxemia/ hypercapnia (early in course of disease: hypocapnia with tachypnea may be present)
    • pCO2 reaches respiratory failure levels when VC falls to <50% of normal (or when respiratory muscle strength falls to <25-30% of normal)
  • PFT’s: restrictive
    • Decreased FEV1 (with normal or increased FEV1/ FVC ratio): FEV1 curve may be truncated near RV when expiratory muscle weakness is severe
    • Decreased VC (due to muscle weakness, decreased lung and chest wall compliance)
    • Decreased TLC
    • Increased RV (inversely related to MEP)
    • Normal-decreased FRC
    • Slightly increased Raw (with normal-increased specific airway conductance)
    • Normal DLCO (especially if it is corrected for decrease in TLC)
    • Decreased MVV (usually): directly related to respiratory muscle strength
    • Decreased MIP/MEP (usually decreased to same degree): most reliable tests (spirometry may be normal early, but MIP/ MEP are usually abnormal)
    • Decreased lung compliance (due to chronically low lung volumes: microatelectasis/ reduced surface tension/ altered interstitial elastic fibers)
    • Transdiaphragmatic pressure: using NG balloon (Pga-Pes)/ normal change >25 cm H2O (referenced to TLC), usually 2-20 cm H2O in bilateral paralysis
  • CXR/Chest CT Pattern: may demonstrate low lung volumes
  • EMG: dennervation potentials/giant motor units
  • NCV: normal

Clinical

  • Exertional Dyspnea
  • Fatigue
  • Tachypnea (typically rapid and shallow)
  • Accessory Muscle Use
  • Fasciculations
  • Spasticity
  • Acute/Chronic Hypoventilation (see Acute Hypoventilation, [[Acute Hypoventilation]] and Chronic Hypoventilation, [[Chronic Hypoventilation]])
  • Respiratory Failure (due to progressively smaller VT with increased VD/VT ratio): may be preceded by sleep disturbance/morning headache/daytime somnolence
  • Aspiration Pneumonia

Treatment

  • Oxygen: for hypoxemia (to prevent polycythemia/ cor pulmonale/ cognitive dysfunction/ respiratory muscle fatigue
  • Ventilatory stimulants (Progesterone/ Diamox/ Doxapram): not usually useful (drive is intact, but response is impaired)
  • Glossopharyngeal breathing: use of tongue/ cheek/ laryngeal/ pharyngeal muscles to inject boluses of air into trachea (permits some speech/ limited cough/ deep breaths to prevent atelectasis)
    • Useful only for hours
    • Increases VC (by up to 1 L), TLC, peak expiratory flow rates, lung compliance/ relieves dyspnea/ improves V/Q matching/ improves cough
  • Inspiratory muscle training
  • Cough/secretions: “cough machine mask”/ abdominal compression techniques/ suctioning/ B2 agonists, mucolytics (aid clearance)/ FOB/ Chest PT/postural drainage
  • Tracheostomy: allows suctioning but decreases ability to generate pressures to clear small airways
  • Mechanical ventilation: may be necessary

Prognosis

  • Average life expectancy after onset of symptoms is 3-4 years

References

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