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)
Respiratory Failure (due to progressively smaller VT with increased VD/VT ratio): may be preceded by sleep disturbance/morning headache/daytime somnolence
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)
