Lambert-Eaton Myasthenic Syndrome (LEMS)

Epidemiology

  • Rare disorder

Etiology

  • Small Cell Lung Cancer:
    • Small cell lung cancer is present in 50% of LEMS cases
    • 6% of small cell lung cancer cases have LEMS (however, when investigated further, about 44% have neuromuscular or autonomic deficits)

Physiology

  • IgG autoantibody against presynaptic calcium channels (Anti-Presynaptic P/Q Voltage-Gated Calcium Channel (VGCC)) -> blocks calcium influx presynaptic nerve terminal -> impaired Ach release at NMJ -> NMJ defect -> chronic hypoventilation

Diagnosis

PFT (restrictive pattern):
-Decreased VC (due to muscle weakness, decreased lung compliance, and decreased chest wall compliance): predicts need for mechanical ventilation
-Decreased TLC
-Increased RV (due to inability to overcome recoil of chest wall outward at volumes below FRC)
-Decreased MIP/MEP/MVV
-Decreased lung compliance (due to chronically low lung volumes: microatelectasis/reduced surface tension/alteration in elastic fibers in lung interstitium)

CXR/Chest CT Pattern:
-May demonstrate aspiration pneumonia and/or low lung volumes

Anti-Presynaptic P/Q Voltage-Gated Calcium Channel (VGCC) Ab:
-Positive in 44-90% of all LEMS cases
-Positive in 10-42% of all small cell lung cancer cases (even when they do not have LEMS)

Muscle Bx: not useful

Tensilon Test: not usually definitive in LEMS (but usually diagnostic in MG)

Repetitive Nerve Stimulation: results in increased compound muscle action potentials (in contrast to MG, where it leads to decreased action potentials)


Clinical

Symptoms/Signs: neurologic symptoms can precede the diagnosis of small cell cancer by up to 2 years in some cases
1) Muscle Weakness: usually slowly progressive proximal muscle weakness (diaphragm is often involved)
– Acute/ChronicHypoventilation (see Acute Hypoventilation, [[Acute Hypoventilation]] and Chronic Hypoventilation, [[Chronic Hypoventilation]])
–Symptoms are usually worse in the morning and improve throughout the day
–Improves with repeated testing (unlike MG)
–Extraocular involvement is uncommon (although ptosis occurs in >50% of small cell-associated cases):
2) Hyporeflexia/Areflexia (>90% of cases): unlike MG
3) Cholinergic Autonomic Manifestations: dry mouth/impotence/constipation/pupillary abnormalities

Complications:
1) Pulmonary HTN/Cor Pulmonale: due to hypoxia/acidosis with resultant pulmonary vasoconstriction


Treatment

Treat Underlying Disease:
-Produces improvement in LEMS

Cholinesterase Inhibitors: usually helpful only in mild disease

Guanidine HCL: may be useful
-Inihibits organelle uptake of calcium, increasing calcium in nerve terminal
-Has serious SE (which may be minimized by using in combo with cholinesterase inhibitors)

Plasmapheresis: produces rapid, but transitory improvement

IVIG: produces rapid, but transitory improvement

Immunosuppressives: may be useful (as in MG)

Aminopyridine Derivatives:
-Effective