Lambert-Eaton myasthenic syndrome

Background

• Disease of the neuromuscular junction leading to primary presentation of weakness
• Caused by auto-antibodies against the voltage-gated calcium channels at the NMJ

Epidemiology

• Predominantly a disease associated with older men with history of cigarette smoking and lung cancer
  • 50% of patients have concurrent small-cell lung cancer
• Syndrome can precede detection of malignancy by several years
• Paraneoplastic syndrome in 60-70% of cases

Clinical Features

• Often presents with alteration in gait or difficulty rising from a chair
• Fluctuating symmetric weakness and fatigue, especially of proximal leg muscles
• Improvement in strength with sustained or repeated exercise (in contrast to MG)
  • Lambert sign: handshake strength increases over several seconds
• Myalgias
• Muscle stiffness (especially in hip and shoulders)
• Paresthesias
• Metallic taste
• Eye movements are unaffected
• Sensory examination normal
• Autonomic dysfunction (dry mouth, erectile dysfunction)
• Compared with myasthenia gravis, LEMS begins with lower extremities weakness and rarely begins with extraocular muscle weakness
• Respiratory failure can occur in late stages of the disease
• Paraneoplastic and autoimmune form of LEMS have similar signs and symptoms

Differential Diagnosis

Weakness

• Neuromuscular weakness
  • Upper motor neuron:
    • CVA
    • Hemorrhagic stroke
    • Multiple sclerosis
    • Amyotrophic Lateral Sclerosis (ALS) (upper and lower motor neuron)
  • Lower motor neuron:
    • Spinal and bulbar muscular atrophy (Kennedy's syndrome)
  • Spinal cord disease:
    • Infection (Epidural abscess)
    • Infarction/ischemia
    • Trauma (Spinal Cord Syndromes)
    • Inflammation (Transverse Myelitis)
      • Acute flaccid myelitis
    • Degenerative (Spinal muscular atrophy)
    • Tumor
  • Peripheral nerve disease:
    • Guillain-Barre syndrome
    • Toxins (Ciguatera)
    • Tick paralysis
    • Diabetic peripheral neuropathy
  • Neuromuscular junction disease:
    • Myasthenia gravis crisis
    • Botulism
    • Organophosphate toxicity
    • Lambert-Eaton myasthenic syndrome
  • Muscle disease:
    • Rhabdomyolysis
    • Dermatomyositis
    • Polymyositis
    • Alcoholic myopathy
• Non-neuromuscular weakness
  • Can't miss diagnoses:
    • ACS
    • Arrhythmia/Syncope
    • Severe infection/Sepsis
    • Hypoglycemia
    • Periodic paralysis (electrolyte disturbance, K, Mg, Ca)
      • Hypokalemic periodic paralysis
      • Thyrotoxic periodic paralysis
    • Respiratory failure
  • Emergent Diagnoses:
    • Symptomatic Anemia
    • Severe dehydration
    • Hypothyroidism
    • Polypharmacy
    • Malignancy
    • Aortic disease - occlusion, stenosis, dissection
  • Other causes of weakness and paralysis
    • Acute intermittent porphyria (ascending weakness)

Evaluation

• Diagnosis is generally a clinical diagnosis
• Confirmation testing for VGCC antibodies
• Neurophysiologic testing

Management

• Supportive (progression to respiratory or bulbar failure is rare)
• Acetylcholinesterase inhibitors (e.g. pyridostigmine) can improve symptoms
• Guanidine
• Aminopyridines: 2-10 mg/day
• IVIG
• Glucocorticoids
• Plasma exchange

Disposition

• Admission required when infectious complications occur or when severe disability requires inpatient immunotherapy
• Referral to rheumatology
• Any patients with risk factors for small cell lung cancer will need to be referred for evaluation of underlying malignancy

See Also

• Myasthenia Gravis