Lambert Eaton Myasthenic Syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is a presynaptic autoimmune neuromuscular disorder with antibodies against voltage gated calcium channels (P/Q type).

• 50 to 60% are paraneoplastic, mostly small cell lung cancer (3% of patients with SCLC); the rest autoimmune with other autoimmune disease.

• Tumour may appear up to 2 to 4 years after onset.

• Older, male, smoker, rapid onset, weight loss and SOX1 antibodies favour cancer.

• Proximal leg weakness, difficulty rising and climbing stairs, improving transiently after exercise.

• Reduced or absent reflexes that facilitate after brief exercise.

• Autonomic: dry mouth, constipation, erectile dysfunction, orthostatic hypotension.

• Mild ptosis, bulbar and respiratory weakness less than MG.

• P/Q type voltage gated calcium channel antibodies (85 to 90%).

• Nerve conduction: low resting CMAP amplitude, incremental response over 100% after 10 seconds of exercise or high rate (20 to 50 Hz) stimulation.

• SOX1 antibodies and cancer screening: CT chest/abdomen/pelvis, FDG PET CT, bronchoscopy; repeat every 6 months for 2 years (then yearly up to 4 years) if negative.

• Exclude myasthenia gravis, myopathy, Guillain-Barre.

• Treat underlying cancer (chemotherapy, radiotherapy); neurological improvement often follows.

• 3,4-diaminopyridine (amifampridine) 15 to 20 mg daily in divided doses, up to 60 to 80 mg daily (watch seizures, QT); add pyridostigmine 30 to 60 mg three to four times daily.

• Immunotherapy: prednisolone 0.5 to 1 mg/kg with azathioprine 2 mg/kg; IVIG 2 g/kg over 2 to 5 days or plasma exchange for severe weakness; rituximab for refractory disease.

• Smoking cessation.

• Avoid neuromuscular blockers and medications that worsen transmission (aminoglycosides, magnesium).

• Respiratory monitoring.